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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">As terapias de alvo molecular tornaram&#8208;se ferramenta importante para o tratamento de doen&#231;as dermatol&#243;gicas&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Os principais grupos de terapia direcionada para doen&#231;as inflamat&#243;rias da pele s&#227;o os anticorpos monoclonais &#40;mAbs&#41; e os inibidores da Janus Quinase &#40;JAKis&#41;&#44; mas tamb&#233;m existem prote&#237;nas de fus&#227;o produzidas por DNA recombinante&#44; como o etanercepte&#46; Anteriormente chamados de produtos biol&#243;gicos&#44; uma vez que eram sintetizados como produtos de organismos vivos&#44; atualmente essas terapias tamb&#233;m s&#227;o compostas de pequenas mol&#233;culas &#8211; portanto&#44; os termos terapia direcionada ou terapia&#8208;alvo devem ser preferidos&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">2</span></a> Al&#233;m disso&#44; o termo moduladores imunol&#243;gicos direcionados &#233; utilizado em livros de refer&#234;ncia&#46;<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O mecanismo de a&#231;&#227;o &#233; heterog&#234;neo entre as diferentes mol&#233;culas&#44; mas todas elas modulam o sistema imunol&#243;gico por meio de impulsos estimulat&#243;rios ou inibit&#243;rios&#44; atuando em pontos espec&#237;ficos das vias de sinaliza&#231;&#227;o da inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">4</span></a> Sua efic&#225;cia e perfil de seguran&#231;a s&#227;o frequentemente hom&#243;logos aos agentes imunossupressores sist&#234;micos padr&#227;o ou at&#233; melhores&#46; Como todos os novos medicamentos&#44; eles n&#227;o est&#227;o isentos de eventos adversos &#40;EA&#41; e seu custo representa barreira importante para sua acessibilidade&#46;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Os primeiros exemplos de terapias imunol&#243;gicas direcionadas para doen&#231;as inflamat&#243;rias em dermatologia foram os ensaios cl&#237;nicos de alefacepte&#44;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">6</span></a> efalizumabe&#44;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">7</span></a> etanercepte<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">8</span></a> e infliximabe<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">9</span></a> para psor&#237;ase no in&#237;cio dos anos 2000&#46; Alefacepte e efalizumabe foram substitu&#237;dos por mol&#233;culas mais novas com renova&#231;&#227;o constante dos medicamentos utilizados em terapias imunol&#243;gicas direcionadas para diferentes doen&#231;as inflamat&#243;rias da pele &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Esta revis&#227;o narrativa tem como objetivo atualizar&#44; resumir e priorizar a grande quantidade de informa&#231;&#245;es sobre importantes doen&#231;as inflamat&#243;rias cut&#226;neas em formato pr&#225;tico para uso na cl&#237;nica&#46; Indica&#231;&#245;es de uso s&#227;o sugeridas considerando dados atuais sobre efic&#225;cia&#44; dose e perfil de seguran&#231;a da imunoterapia direcionada&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Material e m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Esta revis&#227;o foi realizada com base nas diretrizes <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews and Meta&#8208;analyses</span> &#40;PRISMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">10</span></a> Foi feita pesquisa sistem&#225;tica no banco de dados Pubmed nos &#250;ltimos 10 anos &#40;janeiro de 2012 a julho de 2023&#59; estrat&#233;gia de busca&#44; ver Material Suplementar 1&#41;&#46; As refer&#234;ncias de todos os estudos inclu&#237;dos tamb&#233;m foram avaliadas para identificar quaisquer estudos eleg&#237;veis adicionais&#46; Foram selecionadas revis&#245;es sistem&#225;ticas e ensaios cl&#237;nicos randomizados &#40;RCE&#44; em ingl&#234;s&#41;&#46; Tamb&#233;m foram inclu&#237;dos relatos de casos e s&#233;ries de casos&#44; se realizados em humanos&#46; Os estudos foram exclu&#237;dos se o produto biol&#243;gico utilizado estivesse no contexto da medicina alternativa ou se a qualidade do relato fosse considerada insuficiente&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Extra&#231;&#227;o de dados</span><p id="par0035" class="elsevierStylePara elsevierViewall">Os t&#237;tulos e resumos de todos os artigos foram selecionados de maneira independente para elegibilidade por dois autores &#40;E&#46;L&#46; e C&#46;L&#46;&#41;&#46; Os textos completos dos artigos considerados potencialmente eleg&#237;veis foram avaliados criticamente e avaliados quanto &#224; elegibilidade&#46; Qualquer desacordo sobre a inclus&#227;o ou exclus&#227;o de um artigo entre os dois investigadores foi analisado por um terceiro investigador &#40;RC&#41; para chegar a um consenso&#46; Os dados extra&#237;dos de cada estudo inclu&#237;ram dados de cita&#231;&#227;o &#40;t&#237;tulo do estudo&#44; autores&#44; ano de publica&#231;&#227;o&#41;&#44; desenho do estudo &#40;objetivo do estudo&#44; per&#237;odo&#44; cen&#225;rio&#41; e resultados &#40;demografia da popula&#231;&#227;o&#44; medidas de desfecho&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Busca na literatura</span><p id="par0040" class="elsevierStylePara elsevierViewall">Foram identificados 1&#46;360 artigos n&#227;o duplicados com a estrat&#233;gia de busca inicial&#46; A revis&#227;o do t&#237;tulo e do resumo excluiu 1&#46;150&#44; enquanto a revis&#227;o do texto completo excluiu 50 artigos adicionais&#46; Foram inclu&#237;dos 143 estudos nesta revis&#227;o&#44; como descrito no fluxograma PRISMA &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Psor&#237;ase</span><p id="par0045" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a cut&#226;nea cr&#244;nica imunomediada que afeta aproximadamente 1&#37; da popula&#231;&#227;o mundial&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">11&#8211;13</span></a> Apesar de evid&#234;ncias convincentes que apoiam o uso de terapias imunol&#243;gicas direcionadas&#44; a sele&#231;&#227;o de medicamento espec&#237;fico pode ser desafiadora&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">14</span></a> A decis&#227;o final do tratamento deve incluir a prefer&#234;ncia do paciente e&#44; eventualmente&#44; a consulta com m&#233;dicos de outras especialidades para equilibrar riscos e benef&#237;cios&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Crit&#233;rios de eligibilidade</span><p id="par0050" class="elsevierStylePara elsevierViewall">Os pacientes devem ser considerados para terapia imunol&#243;gica direcionada em diversas circunst&#226;ncias&#58; se houver psor&#237;ase grave&#44;<a class="elsevierStyleCrossRefs" href="#bib0865"><span class="elsevierStyleSup">15&#8211;17</span></a> definida como envolvimento superior a 10&#37; da &#225;rea de superf&#237;cie corporal &#40;ASC&#41; total&#44; escore PASI &#40;<span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; ou DLQI &#40;<span class="elsevierStyleItalic">Dermatology Life Quality Index</span>&#41; &#62;<span class="elsevierStyleHsp" style=""></span>10 ou comprometimento de locais espec&#237;ficos &#40;m&#227;os&#44; p&#233;s&#44; couro cabeludo&#44; rosto ou &#225;rea genital&#41;&#59; quando a psor&#237;ase causa prurido n&#227;o trat&#225;vel ou tem consequ&#234;ncias emocionais graves com dura&#231;&#227;o da doen&#231;a superior a seis meses&#44;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">15</span></a> ou n&#227;o responde &#224; terapia convencional&#44; ou n&#227;o pode receber terapia sist&#234;mica padr&#227;o em virtude do estado geral do paciente e de comorbidades ou quando o paciente tem doen&#231;a grave&#44; como psor&#237;ase eritrod&#233;rmica&#44; pustulosa ou artrite psori&#225;sica&#46;<a class="elsevierStyleCrossRefs" href="#bib0865"><span class="elsevierStyleSup">15&#8211;17</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Terapia</span><p id="par0055" class="elsevierStylePara elsevierViewall">Existem m&#250;ltiplas imunoterapias direcionadas para a psor&#237;ase&#46; Terapias direcionadas como anti&#8208;TNF&#8208;&#945;&#44; anti&#8208;IL&#8208;17&#44; anti&#8208;IL&#8208;23 e anti&#8208;IL&#8208;12&#47;23 podem atingir PASI&#8208;90 em mais pacientes do que o tratamento sist&#234;mico anterior &#40;p&#46; ex&#46;&#44; ciclosporina e metotrexato&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a> Os tratamentos anti&#8208;IL&#8208;17 &#40;ou seja&#44; ixequizumabe&#44; secuquinumabe e brodalumabe&#41; e anti&#8208;IL&#8208;23 &#40;risanquizumabe&#44; tildrakizumabe e guselcumabe&#41; mostraram propor&#231;&#227;o maior de pacientes que alcan&#231;aram PASI&#8208;90 em compara&#231;&#227;o com todas as interven&#231;&#245;es sist&#234;micas avaliadas na &#250;ltima metan&#225;lise de rede&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Os inibidores de TNF&#8208;&#945; foram os primeiros medicamentos biol&#243;gicos aprovados para o tratamento da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">12&#44;19</span></a> A metan&#225;lise mostra que&#44; nessa classe&#44; o infliximabe tem a maior efic&#225;cia&#44; seguido pelo certolizumabe&#44; adalimumabe e etanercepte&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;19</span></a> A FDA aprovou sequencialmente o etanercepte &#40;2004&#41;&#44; infliximabe &#40;2005&#41;&#44; adalimumabe &#40;2008&#41;&#44; golimumabe &#40;2017&#41; e certolizumabe &#40;2018&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Os inibidores da IL&#8208;17 atingem elimina&#231;&#227;o total da doen&#231;a &#40;isto &#233;&#44; PASI&#8208;100&#41; em cerca de metade dos pacientes<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">11&#44;12</span></a> e t&#234;m in&#237;cio de a&#231;&#227;o mais r&#225;pido&#46; Os medicamentos aprovados pela FDA para tratar a psor&#237;ase s&#227;o secuquinumabe &#40;2015&#41;&#44; ixekizumabe &#40;2016&#41; e brodalumabe &#40;2017&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Os inibidores de IL&#8208;23&#44; risanquizumabe e guselcumabe&#44; demonstraram recentemente melhor perfil de efic&#225;cia e seguran&#231;a em compara&#231;&#227;o com o anti&#8208;IL&#8208;17 e regime de dosagem conveniente&#46;<a class="elsevierStyleCrossRefs" href="#bib0890"><span class="elsevierStyleSup">20&#44;21</span></a> Os medicamentos aprovados pela FDA s&#227;o guselcumabe &#40;2017&#41;&#44; tildraquizumabe &#40;2018&#41; e risanquizumabe &#40;2019&#41;&#46; Ustequinumabe &#40;2013&#41; &#233; um mAb que inibe IL&#8208;12 e IL&#8208;23&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">JAKis &#40;deucravacitinibe&#44; peficitinibe&#44; baricitinibe&#44; solcitinibe&#44; itacitinibe&#44; abrocitinibe&#44; brepocitinibe&#44; ruxolitinibe e tofacitinibe&#41; tamb&#233;m t&#234;m sido utilizados para o tratamento de pacientes psori&#225;sicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0900"><span class="elsevierStyleSup">22&#44;23</span></a> Embora ainda n&#227;o haja dados completos sobre o impacto cl&#237;nico final no tratamento da psor&#237;ase&#44; ensaios recentes mostram resposta melhor do que certas terapias convencionais &#40;p&#46; ex&#46;&#44; metotrexato&#44; ciclosporina&#41;&#44; mas inferior &#224; terapia imunol&#243;gica direcionada &#40;p&#46; ex&#46;&#44; risanquizumabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a> O deucravacitinibe<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">24&#44;25</span></a>&#44; um inibidor alost&#233;rico seletivo da tirosina quinase 2 &#40;TYK2&#41;&#44; &#233; o &#250;nico JAKi aprovado pela FDA &#40;2022&#41;&#44; alcan&#231;ando PASI&#8208;75 de 70&#37; na semana 24&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos &#40;2004&#8208;2020&#41; foram publicadas 51 diretrizes cl&#237;nicas abordando o tratamento da psor&#237;ase&#44; e 41 delas mencionam o uso de produtos biol&#243;gicos&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">26</span></a> Durante o per&#237;odo de 2021&#8208;2022&#44; v&#225;rias sociedades dermatol&#243;gicas atualizaram suas diretrizes cl&#237;nicas considerando a aprova&#231;&#227;o de novas mol&#233;culas pelas ag&#234;ncias reguladoras de medicamentos&#46;<a class="elsevierStyleCrossRefs" href="#bib0925"><span class="elsevierStyleSup">27&#8211;33</span></a> As diretrizes reconhecem medicamentos anti&#8208;IL&#8208;23 e anti&#8208;IL&#8208;17 como parte dos tratamentos de primeira linha para o manejo da psor&#237;ase&#46; H&#225; grande preocupa&#231;&#227;o em rela&#231;&#227;o a seu alto custo e acessibilidade&#46; A decis&#227;o final para a sele&#231;&#227;o de um medicamento para o tratamento do paciente psori&#225;sico depende de diversos fatores cl&#237;nicos e epidemiol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Perfil de seguran&#231;a da imunoterapia direcionada para psor&#237;ase</span><p id="par0085" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a da imunoterapia direcionada para psor&#237;ase est&#225; bem descrito&#59; os EA mais comuns s&#227;o as infec&#231;&#245;es do trato respirat&#243;rio superior e rea&#231;&#245;es no local da inje&#231;&#227;o para todas as classes de medicamentos&#46;<a class="elsevierStyleCrossRefs" href="#bib0960"><span class="elsevierStyleSup">34&#44;35</span></a> Considera&#231;&#245;es gerais devem ser tomadas em rela&#231;&#227;o &#224; reativa&#231;&#227;o de tuberculose e hepatites B e C&#46; O uso de JAKis tamb&#233;m deve considerar infec&#231;&#245;es anteriores por membros da fam&#237;lia Herpesv&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">As evid&#234;ncias atuais mostram que a imunoterapia direcionada n&#227;o aumenta o risco de EA cardiovasculares importantes&#44; como infarto do mioc&#225;rdio&#44; acidente vascular encef&#225;lico ou morte cardiovascular ou a incid&#234;ncia de neoplasias malignas&#46;<a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">35&#44;37&#8211;39</span></a>Rea&#231;&#227;o adversa cut&#226;nea comum &#233; a mudan&#231;a fenot&#237;pica de psor&#237;ase para eczema at&#243;pico&#44; que ocorre em at&#233; 1&#37;&#8208;12&#44;1&#37; dos pacientes que tomam medicamentos anti&#8208;TNF&#8208;&#945; ou anti&#8208;IL&#8208;17&#47;IL&#8208;23&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">40</span></a> O tratamento t&#243;pico foi bem&#8208;sucedido em alguns casos&#44; mas em outros o tratamento biol&#243;gico precisa ser interrompido&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Rea&#231;&#227;o paradoxal &#8211; piora da psor&#237;ase e&#47;ou novas les&#245;es psori&#225;sicas &#8211; foi relatada com o uso de certos medicamentos &#40;p&#46; ex&#46;&#44; medicamentos anti&#8208;TNF&#8208;&#945; e ustequinumabe&#41;&#46; Essas rea&#231;&#245;es geralmente n&#227;o exigem a interrup&#231;&#227;o da terapia e s&#227;o autolimitadas&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">37</span></a> Outras rea&#231;&#245;es adversas relevantes com a classe anti&#8208;TNF&#8208;&#945; s&#227;o infec&#231;&#227;o do trato urin&#225;rio&#44; dor nas costas&#44; artralgia&#44; prurido e erisipela&#44; e infec&#231;&#245;es f&#250;ngicas invasivas&#44; linfoma&#44; insufici&#234;ncia card&#237;aca&#44; citopenia&#44; indu&#231;&#227;o ou exacerba&#231;&#227;o de doen&#231;a desmielinizante e s&#237;ndrome semelhante a l&#250;pus &#40;p&#46; ex&#46;&#44; infliximabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">40</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Os medicamentos anti&#8208;IL&#8208;17 e anti&#8208;IL&#8208;12&#47;23 t&#234;m menos dados sobre seu perfil de seguran&#231;a&#46; Uma rea&#231;&#227;o adversa de interesse nos inibidores de IL&#8208;17 e IL&#8208;12&#47;23 &#233; a candid&#237;ase mucocut&#226;nea &#40;1&#44;7&#37; em pacientes tratados com secuquinumabe&#44; 3&#44;3&#37; com ixequizumabe&#44; 4&#44;0&#37; com brodalumabe e 2&#44;3&#37; de ustequinumabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">41</span></a> Epis&#243;dios de exacerba&#231;&#227;o de doen&#231;a inflamat&#243;ria intestinal tamb&#233;m foram observados com o uso desses medicamentos&#46; Pacientes com hist&#243;ria de doen&#231;a de Crohn ou colite ulcerativa devem ser tratados com outra imunoterapia direcionada&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">37</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Para os JAKis&#44; os EA mais comuns foram reativa&#231;&#227;o de herpes simples&#44; &#250;lceras bucais&#44; pneumonia&#44; COVID&#8208;19&#44; neoplasias malignas&#44; incluindo linfoma&#44; rabdomi&#243;lise&#44; aumento da creatina fosfoquinase&#44; aumento dos triglicer&#237;deos e aumento das transaminases&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Com os dados dispon&#237;veis&#44; as taxas de qualquer EA foram as mais baixas para tildraquizumabe&#44; certolizumabe e etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">34</span></a> Para EA graves&#44; os mais baixos foram para certolizumabe&#44; risanquizumabe e etanercepte&#46; No tratamento de longo prazo&#44; o risanquizumabe apresentou o perfil de risco&#8208;benef&#237;cio mais favor&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Popula&#231;&#245;es especiais</span><p id="par0115" class="elsevierStylePara elsevierViewall">Gr&#225;vidas&#58; o &#250;nico mAb aprovado pela FDA para uso em pacientes gr&#225;vidas &#233; o certolizumabe pegol&#46; &#201; um fragmento peguilado da por&#231;&#227;o Fab dirigido contra o TNF&#8208;&#945; que n&#227;o atravessa a membrana placent&#225;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">12&#44;19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Pedi&#225;trica&#58; Os mAbs autorizados pela FDA para crian&#231;as &#62;<span class="elsevierStyleHsp" style=""></span>4 anos s&#227;o etanercepte e adalimumabe&#44; secuquinumabe a partir dos 6 anos e ustequinumabe a partir dos 12 anos&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;19&#44;42</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Dermatite at&#243;pica</span><p id="par0125" class="elsevierStylePara elsevierViewall">A dermatite at&#243;pica &#40;DA&#41; &#233; doen&#231;a inflamat&#243;ria cut&#226;nea cr&#244;nica e recidivante que afeta 2&#37;&#8208;5&#37; dos adultos e 20&#37; das crian&#231;as&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">43</span></a> A efic&#225;cia da terapia imunol&#243;gica direcionada na DA foi comprovada por v&#225;rios estudos&#46; Uma revis&#227;o sistem&#225;tica recente de 60 ensaios cl&#237;nicos realizados em 16&#46;579 pacientes confirma a efic&#225;cia cl&#237;nica dessas terapias direcionadas na DA&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Crit&#233;rios de elegibilidade</span><p id="par0130" class="elsevierStylePara elsevierViewall">Tanto crian&#231;as quanto adultos podem ser considerados para receber terapia imunol&#243;gica direcionada se tiverem doen&#231;a grave&#44; definida como envolvimento de mais de 10&#37; da ASC total&#44; Avalia&#231;&#227;o Global do Investigador &#40;IGA&#41; de pelo menos 3&#44; escore EASI &#40;<span class="elsevierStyleItalic">Eczema Area and Severity Index</span>&#41; &#8805; 16&#44; escore SCORAD &#40;<span class="elsevierStyleItalic">Scoring Atopic Dermatitis</span>&#41; &#8805; 50 e escore de gravidade da <span class="elsevierStyleItalic">Pruritus Numerical Rating Scale</span> &#40;PP&#8208;NRS&#41; &#8805; 4&#44; ou quando o prurido &#233; intrat&#225;vel ou tem consequ&#234;ncias emocionais graves&#46;<a class="elsevierStyleCrossRefs" href="#bib1015"><span class="elsevierStyleSup">45&#44;46</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Terapia</span><p id="par0135" class="elsevierStylePara elsevierViewall">Est&#227;o dispon&#237;veis m&#250;ltiplas terapias direcionadas para a DA que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; O dupilumabe demonstrou efic&#225;cia semelhante &#224; ciclosporina em doses mais altas em pacientes com mais de 6 meses de idade&#44; com resposta mais confi&#225;vel e superioridade ao metotrexato e &#224; azatioprina&#44; e consideravelmente menos efeitos adversos&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Isso tornou a terapia imunol&#243;gica direcionada muito promissora na DA&#44; mas a compara&#231;&#227;o da efic&#225;cia e seguran&#231;a entre as terapias direcionadas &#233; dif&#237;cil&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;47</span></a> Quatro medicamentos sist&#234;micos foram aprovados pela FDA &#40;dupilumabe&#44;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">48</span></a> traloquinumabe&#44;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">49</span></a> abrocitinibe<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">50</span></a> e upadacitinibe<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">51</span></a>&#41; e outros medicamentos est&#227;o sendo usados <span class="elsevierStyleItalic">off&#8208;label</span> ou em ensaios cl&#237;nicos&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Em compara&#231;&#227;o com dupilumabe&#44; o abrocitinibe&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; e upadacitinibe&#44; 30<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; foram associados a redu&#231;&#245;es mais altas nos escores EASI&#44; enquanto com baricitinibe e traloquinumabe&#44; as redu&#231;&#245;es nos escores EASI foram semelhantes ou ligeiramente piores do que com dupilumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Dupilumabe &#233; mAb anti&#8208;IL&#8208;4&#47;13 aprovado pela FDA em 2017 para o tratamento de DA moderada a grave&#44; a partir dos 6 meses de idade&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">52</span></a> O efeito terap&#234;utico do dupilumabe &#233; mediado principalmente pela inibi&#231;&#227;o da subunidade alfa do receptor da IL&#8208;4 &#40;IL&#8208;4R&#945;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">53&#44;54</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Traloquinumabe &#233; mAb anti&#8208;IL&#8208;13 aprovado pela FDA em 2021 para o tratamento de DA moderada a grave em adultos&#46; Em dois ECRs&#44; 300<span class="elsevierStyleHsp" style=""></span>mg de traloquinumabe a cada duas semanas alcan&#231;ou escore EASI&#8208;75 em 25&#37;&#8208;33&#44;2&#37; dos pacientes em 16 semanas de tratamento&#46; Esses ECRs tamb&#233;m mostraram melhoras precoces no prurido&#44; interfer&#234;ncia no sono e escore DLQI&#46; Os pacientes mantiveram essas respostas ap&#243;s 52 semanas de tratamento com traloquinumabe sem qualquer medica&#231;&#227;o de resgate&#46;<a class="elsevierStyleCrossRefs" href="#bib1035"><span class="elsevierStyleSup">49&#44;55</span></a> Lebriquizumabe&#44; mAb que tem como alvo a IL&#8208;13 foi avaliado em dois ensaios de fase 3 randomizados&#44; duplo&#8208;cegos&#44; controlados por placebo&#44; em pacientes maiores de 12 anos com DA moderada a grave mostrando escore EASI&#8208;75 em 58&#44;8&#37; e 52&#44;1&#37; dos pacientes&#44; respectivamente&#44; na semana 16&#46;<a class="elsevierStyleCrossRef" href="#bib1070"><span class="elsevierStyleSup">56</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">O abrocitinibe &#233; inibidor de JAK&#8208;1 aprovado pela FDA em 2022 para o tratamento de DA em adultos&#46; Na DA moderada a grave&#44; o abrocitinibe mostrou respostas consistentes no tratamento e n&#227;o apresentou novas preocupa&#231;&#245;es de seguran&#231;a em compara&#231;&#227;o com o dupilumabe&#46;<a class="elsevierStyleCrossRefs" href="#bib1020"><span class="elsevierStyleSup">46&#44;57&#8211;59</span></a> Ele &#233; utilizado na dose de 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; atingindo 70&#37; do escore EASI&#8208;75 na semana 12 de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">58</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Upadacitinibe &#233; um inibidor de JAK&#8208;1 aprovado pela FDA &#40;2022&#41; para o tratamento de DA em pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos&#46; Ele mostra uma melhora no escore EASI&#8208;75 de 71&#37; na semana 16 com uma dose de 30<span class="elsevierStyleHsp" style=""></span>mg&#47;dia por via oral&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">60</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Recentemente&#44; o baricitinibe&#44; um inibidor de primeira gera&#231;&#227;o de JAK 1&#8208;2 ainda n&#227;o aprovado pela FDA na DA&#44; completou ECR de fase 2 e 3 em combina&#231;&#227;o com corticosteroides t&#243;picos em adultos com DA moderada a grave&#46; Na semana 16&#44; o baricitinibe 4<span class="elsevierStyleHsp" style=""></span>mg proporcionou melhora de 54&#44;9&#37; e 59&#44;4&#37; no escore EASI no BREEZE&#8208;AD1 e BREEZE&#8208;AD2&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">61</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Tezepelumabe &#233; mAb humano que se liga &#224; linfopoietina estromal do timo &#40;TSLP&#44; citocina derivada de c&#233;lulas epiteliais que induz a produ&#231;&#227;o de citocinas Th2&#44; incluindo IL&#8208;4&#44; IL&#8208;5 e IL&#8208;13&#41;<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">62</span></a> usado no tratamento da asma&#46; Ele foi testado em doses de 280<span class="elsevierStyleHsp" style=""></span>mg a cada duas semanas em estudos de fase 2&#44; alcan&#231;ando escore EASI&#8208;50 em 65&#37; dos pacientes na 12&#170; semana de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">63</span></a> Fezaquinumabe&#44; mAb humano contra IL&#8208;22&#44; est&#225; em estudos de fase 2&#46; Doses de indu&#231;&#227;o de 600<span class="elsevierStyleHsp" style=""></span>mg seguidas de 300<span class="elsevierStyleHsp" style=""></span>mg a cada duas semanas demonstraram melhora no escore IGA a partir de 12 semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">64</span></a> Nemolizumabe &#233; mAb anti&#8208;IL&#8208;31RA experimentado em estudos de fase 2&#46; Foi relatado que 42&#37; dos pacientes tratados apresentaram melhora no escore EASI ap&#243;s 12 semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">65</span></a> O etoquimabe &#233; outro mAb experimental que se liga &#224; IL&#8208;33 em fase inicial de desenvolvimento&#46; No momento&#44; os estudos testaram doses de 300<span class="elsevierStyleHsp" style=""></span>mg IV uma vez&#44; alcan&#231;ando escore EASI&#8208;50 em 100&#37; dos participantes em 140 dias&#46;<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">66</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Novas terapias imunol&#243;gicas t&#243;picas direcionadas para DA apareceram recentemente como ferramentas terap&#234;uticas&#46; O creme de ruxolitinibe 1&#44;5&#37; &#40;aprovado pela FDA em 2021&#41; para pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos mostra melhora de 71&#44;6&#37; no escore EASI ap&#243;s quatro semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">67</span></a> O creme de tofacitinibe 2&#37; mostrou melhora de 82&#37; no escore EASI ap&#243;s quatro semanas de uso e est&#225; aguardando a aprova&#231;&#227;o da FDA&#46;<a class="elsevierStyleCrossRefs" href="#bib1130"><span class="elsevierStyleSup">68&#44;69</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Perfil de seguran&#231;a da imunoterapia direcionada para DA</span><p id="par0180" class="elsevierStylePara elsevierViewall">Os EA mais comuns foram infec&#231;&#245;es do trato respirat&#243;rio superior e rea&#231;&#245;es no local da inje&#231;&#227;o para todas as classes&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;45</span></a> Considera&#231;&#245;es gerais devem ser observadas em rela&#231;&#227;o &#224; reativa&#231;&#227;o de tuberculose&#44; hepatite B e&#44; no caso de JAKis&#44; considerar tamb&#233;m infec&#231;&#245;es por membros da fam&#237;lia Herpesv&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib1080"><span class="elsevierStyleSup">58&#44;60</span></a> Outros EA comuns em todas as classes foram sintomas oculares &#40;conjuntivite&#44; ceratite&#44; blefarite&#44; prurido ocular&#44; ressecamento e desconforto ocular&#41;&#46; Dupilumabe e traloquinumabe n&#227;o requerem monitoramento laboratorial&#44; mas abrocitinibe&#44; baricitinibe e upadacitinibe necessitam de seguimento laboratorial&#46; Eles podem induzir eleva&#231;&#227;o da creatinofosfoquinase&#44; trombocitopenia e neutropenia&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">45</span></a> Outros EA relatados para JAKis s&#227;o n&#225;usea&#44; cefaleia&#44; diarreia&#44; fadiga&#44; acne&#44; dor abdominal e mialgias&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">70</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Recentemente&#44; observou&#8208;se risco aumentado de artrite inflamat&#243;ria soronegativa e psor&#237;ase em pacientes em uso de dupilumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">71</span></a> Com base nas evid&#234;ncias atuais&#44; parece que o uso de anti&#8208;TNF&#8208;&#945; para psor&#237;ase e anti&#8208;IL&#8208;4&#47;13 para DA est&#227;o inversamente relacionados&#46; O bloqueio duplo com dupilumabe est&#225; associado a doen&#231;as psoriasiformes&#44; enquanto medicamentos biol&#243;gicos para psor&#237;ase podem causar mudan&#231;a fenot&#237;pica para eczema&#46;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">72</span></a></p><p id="par0500" class="elsevierStylePara elsevierViewall">Para produtos t&#243;picos&#44; irrita&#231;&#227;o local leve foi o EA mais comum&#46;<a class="elsevierStyleCrossRefs" href="#bib1125"><span class="elsevierStyleSup">67&#44;68</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">N&#227;o existem dados suficientes para determinar se qualquer terapia imunol&#243;gica direcionada &#233; mais segura do que outra para a DA&#46; O abrocitinibe&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; foi associado a 2&#44;6 vezes mais chances de EA graves em compara&#231;&#227;o com dupilumabe&#44; mas com doses mais altas &#40;isto &#233;&#44; abrocitinibe&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#41; as chances foram menores &#40;1&#44;4&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Taxas mais baixas de EA graves foram observadas com dupilumabe em compara&#231;&#227;o com placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Dupilumabe tamb&#233;m est&#225; associado a aumento n&#227;o significante na infec&#231;&#227;o por herpes&#46; A raz&#227;o para a diminui&#231;&#227;o de infec&#231;&#245;es cut&#226;neas&#44; incluindo eczema herp&#233;tico&#44; &#233; desconhecida&#44; mas a melhora na barreira cut&#226;nea e no microbioma causada pela imunoterapia direcionada pode explicar essa observa&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">73</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Hidradenite supurativa</span><p id="par0200" class="elsevierStylePara elsevierViewall">A hidradenite supurativa &#40;HS&#41; &#233; doen&#231;a autoinflamat&#243;ria do fol&#237;culo pilosseb&#225;ceo com preval&#234;ncia variando de 0&#44;05&#37;&#8208;4&#44;1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a> Existem pelo menos nove diretrizes cl&#237;nicas que consideram o uso de produtos biol&#243;gicos no manejo da HS&#46;<a class="elsevierStyleCrossRefs" href="#bib1165"><span class="elsevierStyleSup">75&#8211;83</span></a></p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Crit&#233;rios de eligibilidade</span><p id="par0205" class="elsevierStylePara elsevierViewall">O manejo com imunoterapia direcionada deve ser considerado precocemente em casos graves&#46; As diretrizes internacionais recomendam iniciar tratamento direcionado para HS recalcitrante moderada a grave&#44; definida como est&#225;gio II&#8208;III de Hurley&#44; ou contagem total de abcessos e n&#243;dulos inflamat&#243;rios &#8805; 3 no in&#237;cio do estudo e resposta inadequada ao tratamento com antibi&#243;ticos orais por pelo menos 90 dias&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Terapia</span><p id="par0210" class="elsevierStylePara elsevierViewall">Existem poucas terapias direcionadas para HS que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; O adalimumabe<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a> &#233; o &#250;nico tratamento biol&#243;gico aprovado pela FDA para HS &#40;2015&#41; e &#233; recomendado como medicamento biol&#243;gico de primeira linha em todas as diretrizes&#59; o infliximabe &#233; a segunda op&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a> Anakinra e bermequimabe podem ser considerados ap&#243;s falha dos agentes anti&#8208;TNF&#8208;&#945;&#44; mas as evid&#234;ncias que apoiam sua efic&#225;cia na HS s&#227;o limitadas&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">O adalimumabe mostrou melhora de 41&#44;8&#37; a 58&#44;9&#37; na resposta cl&#237;nica &#224; HS &#40;HiSCR&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Clinical Response</span>&#41; em 50&#37; dos pacientes em 12 semanas&#46;<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a> O infliximabe demonstrou melhora de 25&#37;&#8208;50&#37; no <span class="elsevierStyleItalic">Hidradenitis Suppurativa Severity Index</span> &#40;HSSI&#41; em 60&#37; dos pacientes em oito semanas&#46;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">85</span></a> Outros anti&#8208;TNFs n&#227;o s&#227;o utilizados para tratar a HS&#44; como etanercepte ou golimumabe&#44; em virtude de rea&#231;&#245;es paradoxais de piora ou indu&#231;&#227;o da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib1160"><span class="elsevierStyleSup">74&#44;86</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Os medicamentos anti&#8208;IL&#8208;1 comprovaram sua efic&#225;cia em pequenos ECR controlados por placebo&#46;<a class="elsevierStyleCrossRefs" href="#bib1225"><span class="elsevierStyleSup">87&#44;88</span></a> Anakinra mostrou melhora &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; no <span class="elsevierStyleItalic">Disease Activity Score</span> &#40;DAS&#41; em 78&#37; dos pacientes em 12 semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">87</span></a> O bermequimabe mostrou melhora de 60&#37; no HiSCR em 12 semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">88</span></a> Esses medicamentos devem ser considerados quando os pacientes n&#227;o s&#227;o candidatos &#224; terapia anti&#8208;TNF&#8208;&#945;&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">As diretrizes cl&#237;nicas tamb&#233;m mencionam outros produtos biol&#243;gicos que t&#234;m sido utilizados com sucesso em s&#233;ries de casos para o tratamento da HS &#40;guselcumabe&#44; risanquizumabe&#44; secuquinumabe&#44; bimequizumabe e upadacitinibe&#41;&#44; mas os resultados em pacientes tratados com esses medicamentos baseiam&#8208;se principalmente em relatos de casos isolados&#44; o que n&#227;o &#233; suficiente para recomendar seu uso no ambiente cl&#237;nico&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Perfil de seguran&#231;a da imunoterapia direcionada para HS</span><p id="par0230" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a dos medicamentos anti&#8208;TNF&#8208;&#945; foi discutido em se&#231;&#227;o anterior &#40;ver Psor&#237;ase&#41;&#46; Para os medicamentos anti&#8208;IL&#8208;1&#44; as considera&#231;&#245;es gerais s&#227;o semelhantes entre eles&#46; Os EA mais comuns s&#227;o rea&#231;&#245;es no local da inje&#231;&#227;o e infec&#231;&#245;es do trato respirat&#243;rio superior&#46; Outros EA relatados s&#227;o cefaleia&#44; dor abdominal&#44; diarreia e sintomas semelhantes aos da gripe&#46;<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">89</span></a></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Pioderma gangrenoso</span><p id="par0235" class="elsevierStylePara elsevierViewall">O pioderma gangrenoso &#40;PG&#41; &#233; dermatose neutrof&#237;lica caracterizada por &#250;lceras cut&#226;neas cr&#244;nicas e recorrentes com borda necrol&#237;tica&#44; com incid&#234;ncia estimada de 3&#8208;10&#47;1&#46;000&#46;000 de casos por ano&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a> Atualmente&#44; n&#227;o existem medicamentos aprovados pela FDA para essa doen&#231;a&#46; Recentemente&#44; novas terapias imunol&#243;gicas direcionadas t&#234;m sido utilizadas com algum sucesso para tratar casos refrat&#225;rios de PG&#44; mas ensaios cl&#237;nicos s&#227;o necess&#225;rios para estabelecer a real efic&#225;cia dessas terapias&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#8211;93</span></a></p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Crit&#233;rios de eligibilidade</span><p id="par0240" class="elsevierStylePara elsevierViewall">Sugere&#8208;se considerar a imunoterapia direcionada no PG ap&#243;s estudo completo para estabelecer o diagn&#243;stico dessa condi&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> A doen&#231;a deve ser recalcitrante ou de intensidade moderada a grave &#40;ASC &#62;<span class="elsevierStyleHsp" style=""></span>10&#37;&#44; locais anat&#244;micos complexos ou dor excruciante&#41;&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Terapia</span><p id="par0245" class="elsevierStylePara elsevierViewall">Existem poucas terapias direcionadas para o PG que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46; O medicamento com mais dados para o tratamento do PG &#233; o infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> O infliximabe demonstrou melhora das les&#245;es na quarta semana &#40;20&#47;29 pacientes&#41;&#44; com remiss&#227;o completa em 21&#37; na sexta semana&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> O infliximabe tamb&#233;m tem sido utilizado com sucesso em combina&#231;&#227;o com outros medicamentos &#40;corticosteroides sist&#234;micos orais&#44; azatioprina&#44; micofenolato de mofetil e ciclosporina&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1250"><span class="elsevierStyleSup">92&#44;93&#44;95</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">H&#225; relatos de casos de PG tratados com adalimumabe e etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a> Com base nesses dados observacionais&#44; n&#227;o foram encontradas diferen&#231;as significantes nas taxas de resposta parcial ou completa ao infliximabe&#44; adalimumabe e etanercepte&#46; Em uma revis&#227;o semissistem&#225;tica sobre inibidores de TNF&#8208;&#945;&#44; foi encontrada taxa de resposta parcial de 87&#37; e resposta completa de 67&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a> O corticosteroide e a ciclosporina podem atingir 90&#37; de taxa de resposta parcial e apenas 47&#37; de taxa de resposta completa ap&#243;s seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Medicamentos anti&#8208;IL&#8208;1 tamb&#233;m t&#234;m sido utilizados para tratar PG&#46;<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">91</span></a> H&#225; 29 casos relatados na literatura do uso de anakinra em pacientes com comorbidades como artrite reumatoide&#44; psor&#237;ase e s&#237;ndromes PASH &#40;pioderma gangrenoso&#44; acne e hidradenite supurativa&#41; e PAPA &#40;artrite piog&#234;nica&#44; pioderma gangrenoso e acne&#41; na dose de 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#44;92</span></a> Em um ensaio n&#227;o controlado&#44; canaquinumabe foi usado em cinco pacientes com PG refrat&#225;rio a esteroides&#46; Quatro mostraram redu&#231;&#227;o no tamanho da les&#227;o&#8208;alvo e tr&#234;s alcan&#231;aram remiss&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Outras terapias imunol&#243;gicas direcionadas usadas com sucesso s&#227;o ustequinumabe &#40;anti&#8208;IL&#8208;12&#47;23&#41;<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">97</span></a> e ruxolitinibe &#40;anti&#8208;JAK1&#8208;2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#44;92</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Perfil de seguran&#231;a da imunoterapia direcionada para PG</span><p id="par0265" class="elsevierStylePara elsevierViewall">H&#225; casos relatados de indu&#231;&#227;o paradoxal de PG com o uso de adalimumabe&#44; etanercepte e&#44; em menor n&#250;mero&#44; com infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es adversas espec&#237;ficas do canaquinumabe s&#227;o piora da artrite reumatoide&#44; pirexia&#44; v&#244;mitos&#44; sinusite e artralgia e&#44; para anakinra&#44; ganho ponderal&#44; dor musculoesquel&#233;tica e vertigem&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Urtic&#225;ria espont&#226;nea cr&#244;nica</span><p id="par0275" class="elsevierStylePara elsevierViewall">A urtic&#225;ria espont&#226;nea cr&#244;nica &#40;UEC&#41; &#233; definida pelo aparecimento de p&#225;pulas pruriginosas transit&#243;rias e&#47;ou angioedema por pelo menos seis semanas sem um gatilho reconhec&#237;vel&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">98</span></a> A preval&#234;ncia global de UEC &#233; de 1&#44;1&#37;&#44; de acordo com a Global Burden of Disease&#46;<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">99</span></a></p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Crit&#233;rios de eligibilidade</span><p id="par0280" class="elsevierStylePara elsevierViewall">Adultos e adolescentes com 12 anos ou mais podem ser considerados para terapia imunol&#243;gica direcionada se permanecerem sintom&#225;ticos apesar do tratamento com anti&#8208;histam&#237;nicos H1 at&#233; quatro vezes a dose padr&#227;o&#44; ou se persistirem sintom&#225;ticos com a terapia combinada &#40;anti&#8208;histam&#237;nicos H1 quatro vezes a dose padr&#227;o mais anti&#8208;histam&#237;nicos H2 e&#47;ou antagonista do receptor de leucotrieno&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1280"><span class="elsevierStyleSup">98&#44;100</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Terapia</span><p id="par0285" class="elsevierStylePara elsevierViewall">Existe apenas uma imunoterapia direcionada atualmente aprovada para UEC&#44; e outras op&#231;&#245;es devem ser selecionadas em casos refrat&#225;rios ou no contexto de pesquisa &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a>&#41;&#46; O omalizumabe&#44; um mAb anti&#8208;IgE&#44; foi aprovado pela FDA em 2014 para uso em pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos com UEC&#46; Essa autoriza&#231;&#227;o foi baseada em dois ECRs &#40;ASTERIA I e ASTERIA II&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">101</span></a> ECRs mostraram que&#44; em 40 semanas&#44; 75&#44;3&#37; dos pacientes com UEC obtiveram resposta completa e 14&#44;6&#37; tiveram resposta parcial&#46;<a class="elsevierStyleCrossRef" href="#bib1300"><span class="elsevierStyleSup">102</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0290" class="elsevierStylePara elsevierViewall">O ligelizumabe&#44; um mAb anti&#8208;IgE&#44; ainda est&#225; em estudo&#44; mas ensaios cl&#237;nicos recentes para o tratamento da UEC est&#227;o mostrando efic&#225;cia semelhante ao omalizumabe&#46;<a class="elsevierStyleCrossRefs" href="#bib1305"><span class="elsevierStyleSup">103&#44;104</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Lirentelimabe &#233; mAb de lectina 8 semelhante &#224; imunoglobulina com liga&#231;&#227;o ao &#225;cido antissi&#225;lico &#40;anti&#8208;SIGLEC&#8208;8&#44; um receptor inibit&#243;rio presente em eosin&#243;filos e mast&#243;citos&#41;&#46; A liga&#231;&#227;o ao SIGLEC&#8208;8 induz a morte de eosin&#243;filos&#44; inibe a degranula&#231;&#227;o mediada por IgE dos mast&#243;citos e a s&#237;ntese <span class="elsevierStyleItalic">de novo</span> de prostaglandina D2&#46; Os resultados de um estudo de fase 2 com lirentelimabe para o tratamento de UEC e para o tratamento de urtic&#225;ria induz&#237;vel demonstraram 92&#37; de resposta completa na semana 22 e apenas 36&#37; de resposta completa em pacientes anteriormente refrat&#225;rios ao tratamento com omalizumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">O dupilumabe demonstrou resposta parcial em relatos de casos&#46;<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a> Benralizumabe e mepolizumabe&#44; ambas mol&#233;culas experimentais anti&#8208;IL&#8208;5R e anti&#8208;IL&#8208;5&#44; respectivamente&#44; tamb&#233;m foram utilizados&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">107</span></a> Em ambos os casos&#44; os pacientes tratados apresentaram melhora cl&#237;nica&#46;<a class="elsevierStyleCrossRef" href="#bib1330"><span class="elsevierStyleSup">108</span></a> O secuquinumabe tem sido usado em relatos de casos para o tratamento de UEC em pacientes refrat&#225;rios ao tratamento com anti&#8208;histam&#237;nicos H1 e omalizumabe&#44; mostrando redu&#231;&#227;o significante na atividade da doen&#231;a desde o in&#237;cio&#46;<a class="elsevierStyleCrossRef" href="#bib1335"><span class="elsevierStyleSup">109</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Perfil de seguran&#231;a da imunoterapia direcionada para UEC</span><p id="par0305" class="elsevierStylePara elsevierViewall">Os efeitos adversos mais comuns&#44; mas control&#225;veis&#44; do omalizumabe s&#227;o cefaleia&#44; dor abdominal superior&#44; pirexia e rea&#231;&#227;o local no local da inje&#231;&#227;o&#46; Efeitos adversos mais graves&#44; como rea&#231;&#227;o anafil&#225;tica&#44; s&#237;ncope e angioedema&#44; foram relatados com frequ&#234;ncia inferior a 1&#47;1&#46;000&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">98</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Para o lirentelimabe&#44; os EA mais comuns inclu&#237;ram rea&#231;&#245;es relacionadas &#224; infus&#227;o&#44; nasofaringite e cefaleia&#46; N&#227;o ocorreram EA graves relacionados ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Alopecia areata</span><p id="par0315" class="elsevierStylePara elsevierViewall">Alopecia areata &#40;AA&#41; &#233; doen&#231;a autoimune decorrente da perda do privil&#233;gio imunol&#243;gico do fol&#237;culo piloso&#46; Recentemente&#44; a FDA aprovou o baricitinibe para tratamento de AA &#40;2022&#41; e muitos outros JAKis est&#227;o em estudo avan&#231;ado para aprova&#231;&#227;o&#46;</p><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Crit&#233;rios de eligibilidade</span><p id="par0320" class="elsevierStylePara elsevierViewall">Os pacientes devem ser considerados para tratamento com JAKis se tiverem doen&#231;a moderada ou grave &#40;perda total de cabelos &#8805; 30&#37; do couro cabeludo por pelo menos tr&#234;s a seis meses&#44; medida utilizando o escore da ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> &#91;SALT&#93; ou resposta refrat&#225;ria ao tratamento convencional nos &#250;ltimos seis meses&#41;&#46; N&#227;o h&#225; limita&#231;&#227;o quanto &#224; dura&#231;&#227;o anterior da alopecia e os estudos consideraram pacientes com ampla varia&#231;&#227;o de dura&#231;&#227;o da AA como candidatos ao tratamento com JAKis&#46;<a class="elsevierStyleCrossRefs" href="#bib1340"><span class="elsevierStyleSup">110&#44;111</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Terapia</span><p id="par0325" class="elsevierStylePara elsevierViewall">Existe apenas uma imunoterapia direcionada atualmente aprovada para AA&#44; mas outras op&#231;&#245;es t&#234;m sido utilizadas com sucesso e devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabela 6</a>&#41;&#46; A FDA aprovou o baricitinibe &#40;2022&#41;&#44; um JAK 1&#8208;2i&#44; para o tratamento de AA em adultos&#46; Sua efic&#225;cia foi avaliada em dois ensaios randomizados&#44; duplo&#8208;cegos e controlados por placebo &#40;BRAVE AA&#8208;1 e BRAVE AA&#8208;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a> Os pacientes nesses estudos receberam 2 ou 4<span class="elsevierStyleHsp" style=""></span>mg de baricitinibe por dia&#46; Os resultados finais na semana 36 mostraram resposta adequada de 22&#37; com 2<span class="elsevierStyleHsp" style=""></span>mg e 38&#37; com 4<span class="elsevierStyleHsp" style=""></span>mg Resultados semelhantes foram observados no BRAVE AA&#8208;2 &#40;19&#37; de resposta adequada com 2<span class="elsevierStyleHsp" style=""></span>mg e 35&#37; com 4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a> Tofacitinibe&#44; um JAK 1&#8208;3i&#44; tem sido usado para tratar casos moderados a graves de AA com &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; de perda de cabelo no couro cabeludo em adultos&#44; alcan&#231;ando resposta completa em 20&#37; dos pacientes tratados e 77&#37; de resposta parcial em quatro a 18 meses de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">112</span></a> Em 2023&#44; a FDA aprovou o ritlecitinibe para o tratamento da AA em pessoas com mais de 12 anos com base nos resultados do estudo ALLEGRO&#44; no qual 23&#37; dos pacientes alcan&#231;aram recupera&#231;&#227;o capilar de pelo menos 80&#37; ap&#243;s seis meses de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1355"><span class="elsevierStyleSup">113</span></a> Ruxolitinibe &#233; o &#250;ltimo JAKi usado para o tratamento da AA&#44; atingindo de forma geral resposta em 93&#37; dos pacientes e resposta completa em 21&#37; dos pacientes tratados em seis meses de seguimento&#46;<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">111</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Perfil de seguran&#231;a da imunoterapia direcionada para AA</span><p id="par0330" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a dos medicamentos inibidores de JAK foi extensivamente estudado e&#44; em geral&#44; todos os JAKis utilizados para o tratamento de AA s&#227;o bem tolerados&#46; Infec&#231;&#245;es do trato respirat&#243;rio superior&#44; hipercolesterolemia&#44; creatina fosfoquinase elevada&#44; cefaleia&#44; diarreia e nasofaringite s&#227;o os EA relatados com mais frequ&#234;ncia&#46; Os efeitos adversos menos comuns inclu&#237;ram outras infec&#231;&#245;es&#44; como herpes&#8208;z&#243;ster&#44; herpes&#8208;simples&#44; infec&#231;&#245;es do trato urin&#225;rio e gastroenterite&#46;<a class="elsevierStyleCrossRefs" href="#bib1340"><span class="elsevierStyleSup">110&#8211;112</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Doen&#231;as bolhosas autoimunes</span><p id="par0335" class="elsevierStylePara elsevierViewall">As doen&#231;as bolhosas autoimunes s&#227;o um grupo de doen&#231;as caracterizadas pela produ&#231;&#227;o de autoanticorpos contra mol&#233;culas de ades&#227;o da pele&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> Essa revis&#227;o ir&#225; discutir a imunoterapia direcionada para p&#234;nfigo vulgar &#40;PV&#41;&#44; p&#234;nfigo foli&#225;ceo &#40;PF&#41; e penfigoide bolhoso &#40;PB&#41;&#46;</p><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Crit&#233;rios de eligibilidade</span><p id="par0340" class="elsevierStylePara elsevierViewall">Os pacientes s&#227;o candidatos &#224; imunoterapia direcionada como op&#231;&#227;o de primeira linha em casos de PV&#47;PF moderado a grave de in&#237;cio recente ou em pacientes previamente tratados que n&#227;o alcan&#231;am remiss&#227;o cl&#237;nica com corticosteroides sist&#234;micos ou adjuvantes imunossupressores&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> A gravidade da doen&#231;a deve ser medida por meio do escore do <span class="elsevierStyleItalic">Pemphigus Disease and Area Index</span> &#40;PDAI&#41;&#46; O envolvimento m&#250;ltiplo das mucosas &#40;oral&#44; nasofar&#237;ngea&#44; conjuntival&#44; genital&#41; ou PDAI &#8805;<span class="elsevierStyleHsp" style=""></span>15 s&#227;o considerados doen&#231;a moderada&#46; Pacientes com escore PDAI &#8805;<span class="elsevierStyleHsp" style=""></span>45 ou les&#245;es orais&#44; disfagia e perda ponderal apresentam doen&#231;a grave&#46;<a class="elsevierStyleCrossRefs" href="#bib1365"><span class="elsevierStyleSup">115&#44;116</span></a></p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Terapia</span><p id="par0345" class="elsevierStylePara elsevierViewall">O rituximabe &#233; o &#250;nico medicamento biol&#243;gico aprovado pela FDA &#40;2018&#41; para doen&#231;as bolhosas e &#233; considerado a primeira op&#231;&#227;o terap&#234;utica para PV e PF pelas diretrizes internacionais&#46;<a class="elsevierStyleCrossRef" href="#bib1370"><span class="elsevierStyleSup">116</span></a> Essa aprova&#231;&#227;o foi baseada nos resultados do Rituxi3&#44;<a class="elsevierStyleCrossRef" href="#bib1365"><span class="elsevierStyleSup">115</span></a> no qual 89&#37; dos pacientes com p&#234;nfigo tratados com rituximabe e prednisolona oral estavam livres da doen&#231;a e sem necessidade de qualquer tratamento adicional ap&#243;s 24 meses&#44; em compara&#231;&#227;o com 34&#37; com prednisolona isoladamente&#46; O tratamento com rituximabe tamb&#233;m reduziu a dose de corticosteroides necess&#225;ria para a remiss&#227;o cl&#237;nica&#44; reduzindo os efeitos adversos associados a altas doses de esteroides<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">117</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0035">tabela 7</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><p id="par0350" class="elsevierStylePara elsevierViewall">Efgartigimode &#233; anticorpo IgG1 humano direcionado ao receptor Fc neonatal&#46; O bloqueio do receptor Fc neonatal diminui a disponibilidade de anticorpos IgG patog&#234;nicos e foi testado para o tratamento de PF e PV&#46;<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">118</span></a> Em um ensaio de fase 2&#44; a utiliza&#231;&#227;o isolada de efgartigimode demonstrou controle precoce da doen&#231;a em 90&#37; dos pacientes ap&#243;s 17 dias&#46; Combinado com prednisona&#44; levou &#224; remiss&#227;o cl&#237;nica completa em 64&#37; dos pacientes ap&#243;s seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">119</span></a> Dois ensaios cl&#237;nicos de fase 3 avaliando a efic&#225;cia e a seguran&#231;a do efgartigimode em adultos com p&#234;nfigo &#40;<a href="ctgov:NCT04598451">NCT04598451</a> e <a href="ctgov:NCT04598477">NCT04598477</a>&#41; est&#227;o em andamento&#46;<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">117</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">O fator de ativa&#231;&#227;o de c&#233;lulas B &#40;BAFF&#41;&#44; tamb&#233;m conhecido como estimulador de linf&#243;citos B &#40;BLyS&#41;&#44; &#233; um importante ativador de c&#233;lulas B&#46;<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">120</span></a> O ianalumabe &#233; um mAb experimental que se liga ao BLyS&#46; Um ensaio cl&#237;nico de fase 2 foi conduzido para determinar as doses&#44; o benef&#237;cio e a seguran&#231;a do ianalumabe em pacientes com PV&#44; mostrando diminui&#231;&#227;o de 73&#37; no escore m&#233;dio do PDAI na semana 12 em sete pacientes com p&#234;nfigo em compara&#231;&#227;o com controles tratados com placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">Tratamento com rituximabe&#44; omalizumabe e dupilumabe est&#225; relatado em pacientes com PB&#46; Cao et al&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> conduziram uma revis&#227;o sistem&#225;tica para avaliar o uso desses tr&#234;s produtos biol&#243;gicos em pacientes com PB refrat&#225;rios ao uso de outras terapias sist&#234;micas&#44; como corticosteroides sist&#234;micos&#44; metotrexato&#44; micofenolato de mofetil&#44; azatioprina&#44; ciclosporina e ciclofosfamida&#46; Os autores descobriram que o rituximabe levou &#224; remiss&#227;o completa em 70&#44;5&#37; e &#224; remiss&#227;o parcial em 23&#44;8&#37; dos pacientes ap&#243;s seis meses de seguimento&#44; com taxa de recorr&#234;ncia de 20&#44;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> O omalizumabe levou &#224; remiss&#227;o completa em 67&#44;9&#37; e &#224; remiss&#227;o parcial em 20&#44;8&#37; dos pacientes em seis meses&#44; com taxa de recorr&#234;ncia de 5&#44;7&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> O dupilumabe levou &#224; remiss&#227;o completa em 66&#44;7&#37; e &#224; remiss&#227;o parcial em 19&#44;4&#37; dos pacientes ap&#243;s 4&#44;5 meses de tratamento&#44; com taxa de recorr&#234;ncia de 5&#44;6&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">123&#44;124</span></a></p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Perfil de seguran&#231;a da imunoterapia direcionada para doen&#231;as bolhosas</span><p id="par0365" class="elsevierStylePara elsevierViewall">Embora o rituximabe seja um excelente medicamento para PV ou PF graves&#44; ele tamb&#233;m est&#225; associado a EA graves bem conhecidos&#46; Os mais bem documentados s&#227;o rea&#231;&#245;es &#224; infus&#227;o&#44; infec&#231;&#245;es&#44; dist&#250;rbios card&#237;acos e casos de leucoencefalopatia multifocal progressiva fatal&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> A maioria desses EA pode ser controlada clinicamente se forem reconhecidos no est&#225;gio inicial&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">Um estudo recente mostrou que o tratamento com rituximabe foi associado a menor risco de desenvolvimento de comorbidades cardiovasculares e metab&#243;licas&#44; por isso pode ser particularmente preferido em indiv&#237;duos com fatores de risco cardiovasculares e metab&#243;licos&#44; para os quais os EA relacionados aos corticosteroides devem ser rigorosamente evitados&#46;<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">125</span></a></p></span></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Outras doen&#231;as dermatol&#243;gicas</span><p id="par0375" class="elsevierStylePara elsevierViewall">Ser&#227;o consideradas nesta se&#231;&#227;o doen&#231;as com evid&#234;ncias escassas &#40;pequenos ensaios ou s&#233;ries de casos&#44; evid&#234;ncias indiretas de outras doen&#231;as ou ensaios em andamento sem resultados&#41; ou com terapia t&#243;pica&#44; mas sem terapia sist&#234;mica dispon&#237;vel &#40;<a class="elsevierStyleCrossRef" href="#tbl0040">tabela 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">S&#237;ndrome de Stevens&#8208;Johnson&#47;necr&#243;lise epid&#233;rmica t&#243;xica</span><p id="par0380" class="elsevierStylePara elsevierViewall">A s&#237;ndrome de Stevens&#8208;Johnson&#47;necr&#243;lise epid&#233;rmica t&#243;xica &#40;SSJ&#47;NET&#41; &#233; doen&#231;a mucocut&#226;nea grave e rara causada pela exposi&#231;&#227;o a determinados medicamentos &#8211; os mais frequentes s&#227;o sulfonamidas&#44; anticonvulsivantes&#44; anti&#8208;inflamat&#243;rios n&#227;o esteroides&#44; alopurinol e penicilinas&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Em virtude de sua baixa incid&#234;ncia&#44; o uso relatado de produtos biol&#243;gicos nessa doen&#231;a foi limitado principalmente a s&#233;ries de casos e apenas dois ensaios&#46;<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">126&#8211;128</span></a> Com os dados atuais&#44; a efic&#225;cia e a seguran&#231;a da monoterapia biol&#243;gica e da terapia combinada n&#227;o podem ser determinadas de maneira conclusiva&#44; e o papel final desses medicamentos ainda est&#225; sendo pesquisado&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall">O maior n&#250;mero de casos relatados est&#225; relacionado com o etanercepte&#46; O regime terap&#234;utico mais utilizado &#233; 25<span class="elsevierStyleHsp" style=""></span>mg &#40;em crian&#231;as com peso &#60;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; e 50<span class="elsevierStyleHsp" style=""></span>mg &#40;adultos ou crian&#231;as &#62;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; nos dias 0 e 3&#46; A monoterapia com etanercepte alcan&#231;ou reepiteliza&#231;&#227;o em 13 dias e taxa de mortalidade de 7&#44;6&#37;&#44; enquanto os pacientes tratados com etanercepte em combina&#231;&#227;o com corticosteroides alcan&#231;aram reepiteliza&#231;&#227;o em 11&#44;1 dias e tiveram taxa de mortalidade de 7&#44;7&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Wang et al&#46;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a> conduziram um ECR no qual 96 pacientes com SSJ&#47;NET foram inclu&#237;dos para comparar os efeitos do etanercepte aos corticosteroides tradicionais&#46; O estudo demonstrou que o etanercepte diminuiu a mortalidade prevista com base no escore de gravidade espec&#237;fico para NET &#40;SCORTEN&#41; em cerca de 9&#44;4&#37; em compara&#231;&#227;o aos corticosteroides tradicionais&#46;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a> O infliximabe geralmente era usado na dose de 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Em relatos de casos de pacientes tratados com infliximabe em monoterapia&#44; o n&#250;mero m&#233;dio de dias at&#233; a reepiteliza&#231;&#227;o foi de 10&#44;4 e n&#227;o houve relatos de mortalidade&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Nos relatos de casos de NET tratados com a combina&#231;&#227;o infliximabe&#47;corticosteroides sist&#234;micos&#44; o n&#250;mero m&#233;dio de dias para reepiteliza&#231;&#227;o foi de 14&#44;2 e a taxa m&#233;dia de mortalidade foi de 22&#44;2&#37;&#46; Uma revis&#227;o Cochrane recente mostrou que o etanercepte 25<span class="elsevierStyleHsp" style=""></span>mg &#40;50<span class="elsevierStyleHsp" style=""></span>mg se &#62;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; duas vezes por semana at&#233; a cicatriza&#231;&#227;o das les&#245;es cut&#226;neas pode reduzir a mortalidade espec&#237;fica da doen&#231;a em compara&#231;&#227;o com os corticosteroides &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;51&#59; IC95&#37; 0&#44;16&#8208;1&#44;63&#41;&#46; com poss&#237;veis benef&#237;cios e poss&#237;veis danos&#46;<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">129</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao uso de imunoterapia direcionada utilizada na SSJ&#47;NET em compara&#231;&#227;o aos corticosteroides&#44; n&#227;o houve diferen&#231;a estat&#237;stica observada entre os dois grupos de tratamento na incid&#234;ncia de EA&#59; entretanto&#44; houve menor incid&#234;ncia de hemorragia gastrintestinal relatada com produtos biol&#243;gicos <span class="elsevierStyleItalic">versus</span> corticosteroide tradicional&#46;<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">126&#44;127&#44;130</span></a></p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">DiHS&#47;DRESS</span><p id="par0395" class="elsevierStylePara elsevierViewall">A s&#237;ndrome de hipersensibilidade induzida por medicamentos&#47;rea&#231;&#227;o a medicamentos com eosinofilia e sintomas sist&#234;micos &#40;DiHS&#47;DRESS&#41; &#233; uma rea&#231;&#227;o medicamentosa grave com mortalidade de 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">131</span></a> Casos de sucesso foram publicados usando terapia imunol&#243;gica direcionada&#46; Em um relato recente estudando dois casos de DRESS associado a envolvimento mioc&#225;rdico&#44; tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia foi usado &#40;por tr&#234;s anos&#41; sequencialmente associado a corticosteroides&#44; ciclosporina&#44; metotrexato ou IVIg&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a> Os dois casos demonstraram remiss&#227;o quando o tofacitinibe foi utilizado&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a></p><p id="par0400" class="elsevierStylePara elsevierViewall">Um estudo relato de casos anterior de 10 pacientes com DRESS demonstrou tempo m&#233;dio de cicatriza&#231;&#227;o de 8&#44;5 dias ap&#243;s inje&#231;&#227;o subcut&#226;nea de 50<span class="elsevierStyleHsp" style=""></span>mg de etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">131</span></a> Por fim&#44; h&#225; um &#250;nico relato de caso de paciente tratado com sucesso com mepolizumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">133</span></a></p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">L&#237;quen plano</span><p id="par0405" class="elsevierStylePara elsevierViewall">O adalimumabe &#233; a &#250;nica imunoterapia direcionada recomendada pelas diretrizes internacionais para o tratamento de LP cut&#226;neo e mucoso&#44; em casos refrat&#225;rios graves&#46;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a> Seu uso melhora o prurido e obt&#233;m a cicatriza&#231;&#227;o das les&#245;es cut&#226;neas em um per&#237;odo de seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a> Outra imunoterapia direcionada para LP &#233; o ruxolitinibe t&#243;pico&#44; que est&#225; em estudos de fase 2 para tratar LP cut&#226;neo&#46;<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">135</span></a> Ele foi testado como creme a 1&#44;5&#37; duas vezes ao dia&#44; mostrando melhora no escore cl&#237;nico e escore modificado do <span class="elsevierStyleItalic">Composite Assessment of Index Lesion Severity</span> &#40;mCAILS&#41; ap&#243;s quatro semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">135</span></a> O uso de tofacitinibe foi relatado em s&#233;ries de casos em doses de 5<span class="elsevierStyleHsp" style=""></span>mg &#40;duas vezes ao dia&#41; em per&#237;odos de seguimento variando de dois a nove meses para tratar l&#237;quen plano pilar &#40;LPP&#41; e LP hipertr&#243;fico&#44; mostrando melhora cl&#237;nica e no escore <span class="elsevierStyleItalic">LPP Activity Index</span> &#40;LPPAI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">136</span></a> O relato do uso de outros JAKis&#44; como upadacitinibe ou baricitinibe&#44; &#233; escasso&#46; H&#225; 13 pacientes relatados em s&#233;ries de casos e relatos de casos usando baricitinibe para LPP&#44; com cinco alcan&#231;ando resolu&#231;&#227;o parcial&#44; sete sem resolu&#231;&#227;o e apenas um com resolu&#231;&#227;o completa&#46; H&#225; apenas dois relatos de caso com o uso de upadacitinibe para LP&#44; e ambos obtiveram resolu&#231;&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">137</span></a> Por fim&#44; estudos de fase 2 est&#227;o sendo realizados atualmente com ixequizumabe &#40;LP cut&#226;neo&#44; LPP&#41; e secuquinumabe &#40;LP cut&#226;neo&#44; LPP e LP oral&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1480"><span class="elsevierStyleSup">138</span></a></p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">L&#250;pus eritematoso cut&#226;neo</span><p id="par0410" class="elsevierStylePara elsevierViewall">A FDA aprovou o anifrolumabe para o l&#250;pus eritematoso sist&#234;mico &#40;LES&#41; em julho de 2021&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">139</span></a> O anifrolumabe &#233; anticorpo monoclonal totalmente humanizado que inibe seletivamente o receptor 1 do IFN&#8208;&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">139</span></a> No ECR TULIP&#8208;2&#44; o anifrolumabe foi testado para o tratamento do LES&#44; em pacientes com doen&#231;a cut&#226;nea pelo menos moderadamente grave&#44; e 49&#37; dos pacientes obtiveram redu&#231;&#227;o no escore <span class="elsevierStyleItalic">Cutaneous Lupus Erythematosus Disease Area and Severity Index</span> &#40;CLASI&#41; &#8805; 50&#37; em compara&#231;&#227;o com 25&#37; no grupo placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">140</span></a> O belimumabe &#233; outro medicamento aprovado pela FDA em 2011 para tratamento do LES&#46; Ainda n&#227;o h&#225; resultados finais espec&#237;ficos para a pele em rela&#231;&#227;o a esse medicamento no LEC&#46;<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">141</span></a></p></span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Vitiligo</span><p id="par0415" class="elsevierStylePara elsevierViewall">Para o vitiligo&#44; o ruxolitinibe t&#243;pico foi aprovado pela FDA em 2022 para o tratamento de doen&#231;a n&#227;o segmentar comprometendo &#60;<span class="elsevierStyleHsp" style=""></span>10&#37; da ASC em pacientes adultos e pedi&#225;tricos com &#62;<span class="elsevierStyleHsp" style=""></span>12 anos&#46; Em dois ensaios de fase 3 &#40;TRuE&#8208;V1 e TRuE&#8208;V2&#41;&#44; os indiv&#237;duos foram randomizados para tratamento com ruxolitinibe creme a 1&#44;5&#37; ou placebo duas vezes ao dia durante duas semanas&#46; No final do per&#237;odo de tratamento de 24 semanas&#44; 30&#37; dos pacientes que receberam ruxolitinibe tiveram pelo menos 75&#37; de melhora no <span class="elsevierStyleItalic">Vitiligo Area Scoring Index</span> &#40;VASI&#41; facial&#44; em compara&#231;&#227;o com 10&#37; dos pacientes que receberam placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a> Tamb&#233;m nesses estudos&#44; o creme de ruxolitinibe mostrou melhora na pigmenta&#231;&#227;o acral&#44; o que historicamente tem sido uma &#225;rea refrat&#225;ria &#224; repigmenta&#231;&#227;o com fototerapia&#44; corticosteroides t&#243;picos e tacrolimus&#46;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a> Um estudo piloto com 11 pacientes com vitiligo facial usando creme de tofacitinibe 2&#37; em conjunto com UVB de banda estreita mostrou redu&#231;&#227;o de 70&#37; no escore VASI ap&#243;s dois a quatro meses&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">143</span></a> Por outro lado&#44; uma s&#233;rie de casos de 10 pacientes em uso de tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia por 10 meses e UVB de banda estreita ou fotoexposi&#231;&#227;o obteve diminui&#231;&#227;o de apenas 5&#44;4&#37; na ASC &#40;cinco pacientes&#41; e outros cinco pacientes n&#227;o alcan&#231;aram qualquer repigmenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1510"><span class="elsevierStyleSup">144</span></a></p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Doen&#231;as granulomatosas cut&#226;neas &#40;granuloma anular e sarcoidose&#41;</span><p id="par0420" class="elsevierStylePara elsevierViewall">As doen&#231;as granulomatosas podem representar desafios terap&#234;uticos&#46; O manejo pode ser insatisfat&#243;rio com a terapia sist&#234;mica convencional&#46;<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">145</span></a> O tratamento com anti&#8208;TNF foi tentado com resultados vari&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a> A imunoterapia direcionada para JAKis parece ser op&#231;&#227;o promissora com base nos resultados de s&#233;ries de casos recentes&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a> Tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia foi utilizado em pacientes que n&#227;o responderam aos corticosteroides&#46; Em relato de casos de apenas um paciente&#44; a remiss&#227;o completa foi obtida ap&#243;s quatro meses de tratamento&#46; Para sarcoidose &#40;tr&#234;s pacientes&#41;&#44; a mesma s&#233;rie de casos mostrou resposta completa em dois pacientes e melhora de 96&#37; em um paciente&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a> Mais ECRs s&#227;o necess&#225;rios para estabelecer o valor real dos JAKis nas doen&#231;as granulomatosas&#46;</p></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">S&#237;ndrome hipereosinof&#237;lica</span><p id="par0425" class="elsevierStylePara elsevierViewall">Uma s&#233;rie de casos de cinco pacientes refrat&#225;rios a esteroides tratados com tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia mostrou remiss&#227;o completa em tr&#234;s deles e remiss&#227;o quase completa em outro&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">148</span></a> O paciente restante n&#227;o conseguiu completar o tratamento com tofacitinibe por motivos relacionados ao seguro de sa&#250;de&#44; e o tratamento foi alterado para ruxolitinibe 25<span class="elsevierStyleHsp" style=""></span>mg pela manh&#227; e 10<span class="elsevierStyleHsp" style=""></span>mg &#224; noite&#46; Esse paciente tamb&#233;m obteve remiss&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">148</span></a></p></span><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Morfeia</span><p id="par0430" class="elsevierStylePara elsevierViewall">H&#225; casos de sucesso com uso de imunoterapia direcionada para casos refrat&#225;rios de morfeia&#46; Em dois pacientes com morfeia profunda generalizada associada &#224; fasci&#237;te eosinof&#237;lica que n&#227;o responderam &#224; corticoterapia&#44; tofacitinibe &#40;10<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia&#41; foi adicionado &#224; fototerapia e ao metotrexato&#44; proporcionando melhora cl&#237;nica em ambos&#46;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">149</span></a> Foi relatado que tocilizumabe &#40;um medicamento anti&#8208;IL&#8208;6&#41; &#233; eficaz no tratamento da morfeia panescler&#243;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib1540"><span class="elsevierStyleSup">150&#44;151</span></a> Uma adolescente de 14 anos foi tratada com sucesso com infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">150</span></a></p></span></span></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Conclus&#227;o</span><p id="par0435" class="elsevierStylePara elsevierViewall">Muitas terapias imunol&#243;gicas direcionadas s&#227;o atualmente empregadas no tratamento de doen&#231;as dermatol&#243;gicas inflamat&#243;rias&#46; Algumas dessas mol&#233;culas ganharam papel importante no tratamento de doen&#231;as cut&#226;neas cr&#244;nicas e incapacitantes que n&#227;o eram anteriormente controladas com tratamentos padr&#227;o&#44; como o anti&#8208;IL&#8208;4&#47;13 na DA&#44; o anti&#8208;TNF&#8208;&#945; na HS ou os inibidores de JAK na AA&#44; gerando mudan&#231;a de paradigma no arsenal terap&#234;utico da dermatologia&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;152&#44;153</span></a> Al&#233;m disso&#44; os avan&#231;os na compreens&#227;o da fisiopatologia dessas doen&#231;as facilitaram abordagens terap&#234;uticas direcionadas para vias inflamat&#243;rias&#44; como o bloqueio de citocinas dependentes de JAK&#8208;STAT IL&#8208;5&#44; IL&#8208;6&#44; IL&#8208;10 e IL&#8208;13 em DiHS&#47;DRESS&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">Existem alguns aspectos cr&#237;ticos no desenvolvimento de terapias direcionadas para doen&#231;as inflamat&#243;rias da pele que devem ser considerados&#46; A seguran&#231;a em longo prazo &#233; um aspecto relevante de todos os novos medicamentos&#46; Alguns EA podem permanecer latentes durante os ensaios cl&#237;nicos&#44; aparecendo apenas com o uso prolongado&#46; Outros &#8211; em muito poucos pacientes &#8211; podem surgir desde o in&#237;cio do tratamento&#44; induzindo uma rea&#231;&#227;o paradoxal com piora do quadro cl&#237;nico sob tratamento com imunoterapia direcionada &#40;p&#46; ex&#46;&#44; PG&#44; psor&#237;ase&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0960"><span class="elsevierStyleSup">34&#44;35&#44;90</span></a> A colabora&#231;&#227;o entre ag&#234;ncias reguladoras&#44; profissionais de sa&#250;de e ind&#250;stria farmac&#234;utica &#233; essencial na vigil&#226;ncia p&#243;s&#8208;comercializa&#231;&#227;o e nos estudos de seguimento de longo prazo para avaliar a seguran&#231;a e a efic&#225;cia desses novos medicamentos&#46;<a class="elsevierStyleCrossRef" href="#bib1560"><span class="elsevierStyleSup">154</span></a></p><p id="par0445" class="elsevierStylePara elsevierViewall">Para que um medicamento seja considerado vi&#225;vel&#44; ele deve garantir resultados cl&#237;nicos superiores em compara&#231;&#227;o com os tratamentos existentes&#46; Isso levou os estudos a utilizarem vari&#225;veis clinim&#233;tricas cada vez melhores &#40;p&#46; ex&#46;&#44; PASI&#8208;75 <span class="elsevierStyleItalic">vs</span>&#46; PASI&#8208;90 na psor&#237;ase&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">12</span></a> mas n&#227;o necessariamente a melhores compara&#231;&#245;es&#46; Para comparar a efic&#225;cia entre medicamentos&#44; os pesquisadores realizaram metan&#225;lises em rede&#44; o que fornece algumas informa&#231;&#245;es&#44; mas tem suas limita&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Essa dificuldade de compara&#231;&#227;o direta com os medicamentos antigos ocorre&#44; por exemplo&#44; no caso de JAKi <span class="elsevierStyleItalic">versus</span> metotrexato na DA moderada a grave&#44; JAKi <span class="elsevierStyleItalic">versus</span> NB&#8208;UVB no vitiligo e etanercepte <span class="elsevierStyleItalic">versus</span> prednisona na DRESS&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;44&#44;133&#44;142</span></a> Faltam estudos que avaliem o impacto econ&#244;mico dessas decis&#245;es e que possam ajudar a aumentar o acesso a essas novas terapias&#46;<a class="elsevierStyleCrossRef" href="#bib1565"><span class="elsevierStyleSup">155</span></a></p><p id="par0450" class="elsevierStylePara elsevierViewall">Apesar da efic&#225;cia demonstrada em ensaios e estudos de evid&#234;ncias cl&#237;nicas&#44; as terapias direcionadas ainda s&#227;o subutilizadas&#44; especialmente em regi&#245;es de baixa ou m&#233;dia renda&#44; em virtude da disponibilidade limitada e da cobertura de seguro inadequada&#46; No Chile&#44; por exemplo&#44; 92&#37; da popula&#231;&#227;o n&#227;o t&#234;m cobertura para terapia direcionada para doen&#231;as cut&#226;neas&#44; o que leva a despesas pessoais&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">156</span></a> Situa&#231;&#227;o semelhante &#233; observada no Peru&#44; e condi&#231;&#245;es ligeiramente melhores no Brasil&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">156</span></a> Em uma pesquisa realizada pelo International Psoriasis Council em pa&#237;ses com poucos recursos ou em desenvolvimento&#44; incluindo Argentina&#44; Brasil&#44; Chile&#44; Col&#244;mbia&#44; M&#233;xico&#44; Peru&#44; China&#44; Egito&#44; Ir&#227;&#44; &#205;ndia e &#193;frica do Sul&#44; os dermatologistas geralmente citaram o custo como a principal barreira ao acesso &#224; terapia biol&#243;gica para a psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">157</span></a></p><p id="par0455" class="elsevierStylePara elsevierViewall">A maioria das Diretrizes de Pr&#225;tica Cl&#237;nica &#40;DPC&#41; para doen&#231;as inflamat&#243;rias da pele incorpora uma estratifica&#231;&#227;o l&#243;gica do manejo m&#233;dico em diferentes est&#225;gios da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0930"><span class="elsevierStyleSup">28&#44;45&#44;75&#44;100&#44;116</span></a> Essa estratifica&#231;&#227;o pode n&#227;o refletir com precis&#227;o as condi&#231;&#245;es sociossanit&#225;rias em v&#225;rias regi&#245;es do mundo&#46; A maioria &#40;72&#44;1&#37;&#41; das DPCs dermatol&#243;gicas &#233; origin&#225;ria de pa&#237;ses com alto &#237;ndice sociodemogr&#225;fico &#40;ISD&#41;&#44; enquanto apenas uma pequena propor&#231;&#227;o vem de pa&#237;ses de m&#233;dio&#8208;alto &#40;8&#44;0&#37;&#41;&#44; m&#233;dio &#40;5&#44;3&#37;&#41; e baixo ISD &#40;1&#44;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">158</span></a> Geograficamente&#44; a distribui&#231;&#227;o tamb&#233;m n&#227;o &#233; uniforme&#44; correspondendo a 51&#44;8&#37; na Europa&#44; 21&#44;2&#37; na Am&#233;rica do Norte&#44; 15&#44;5&#37; na &#193;sia&#44; 4&#44;9&#37; na Am&#233;rica Latina e 4&#44;4&#37; na Austral&#225;sia&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">158</span></a> Assim&#44; as DPCs adaptadas &#224;s necessidades regionais nos pa&#237;ses em desenvolvimento ainda s&#227;o escassas e necess&#225;rias para melhor manejo dos pacientes que utilizam terapia direcionada para doen&#231;as inflamat&#243;rias da pele&#46;</p><p id="par0460" class="elsevierStylePara elsevierViewall">Esses novos moduladores imunol&#243;gicos direcionados para o tratamento de doen&#231;as inflamat&#243;rias da pele est&#227;o passando pelas mesmas etapas hist&#243;ricas de desenvolvimento pelas quais muitos medicamentos importantes atualmente em uso passaram&#46; Os dados apresentados e o elevado n&#250;mero de novos manuscritos que aparecem diariamente na literatura m&#233;dica preveem um futuro promissor para a utiliza&#231;&#227;o desses medicamentos no tratamento de doen&#231;as cr&#244;nicas da pele melhorando a qualidade de vida dos pacientes&#46;</p></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Suporte financeiro</span><p id="par0465" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Contribui&#231;&#227;o dos autores</span><p id="par0470" class="elsevierStylePara elsevierViewall">Edinson Lopez&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0475" class="elsevierStylePara elsevierViewall">Raul Cabrera&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0480" class="elsevierStylePara elsevierViewall">Crist&#243;bal Lecaros&#58; Concep&#231;&#227;o e planejamento do estudo&#59; coleta&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Conflito de interesses</span><p id="par0485" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Terapias de alvo molecular&#44; como anticorpos monoclonais &#40;mAbs&#41; e inibidores de Janus Quinase &#40;JAKis&#41;&#44; surgiram como ferramentas essenciais para o tratamento de doen&#231;as dermatol&#243;gicas&#46; Essas terapias modulam o sistema imune por vias de sinaliza&#231;&#227;o espec&#237;ficas&#44; proporcionando alternativas eficazes aos agentes imunossupressores sist&#234;micos tradicionais&#46; Esta revis&#227;o tem como objetivo fornecer um resumo atualizado das terapias imunol&#243;gicas direcionadas para doen&#231;as inflamat&#243;rias da pele&#44; considerando sua fisiopatologia&#44; efic&#225;cia&#44; dosagem e perfis de seguran&#231;a&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A revis&#227;o seguiu as diretrizes <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews and Meta&#8208;analyses</span> &#40;PRISMA&#41;&#46; Uma busca sistem&#225;tica foi conduzida na base de dados PubMed nos &#250;ltimos 10 anos&#44; com foco em ensaios cl&#237;nicos randomizados&#44; relatos de casos e s&#233;ries de casos relacionados a terapias imunol&#243;gicas direcionadas em dermatologia&#46; Crit&#233;rios de elegibilidade foram aplicados e os dados foram extra&#237;dos de cada estudo&#44; incluindo dados de cita&#231;&#245;es&#44; desenho do estudo e resultados&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram identificados 1&#46;360 artigos n&#227;o duplicados com a estrat&#233;gia de busca inicial&#46; A revis&#227;o do t&#237;tulo e do resumo excluiu 1&#46;150&#44; enquanto a revis&#227;o do texto completo excluiu 50 artigos adicionais&#46; A revis&#227;o incluiu 143 estudos publicados entre 2012 e 2022&#44; destacando 39 medicamentos atualmente sob investiga&#231;&#227;o ou em uso para o tratamento de doen&#231;as inflamat&#243;rias da pele&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Limita&#231;&#245;es do estudo</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A heterogeneidade das informa&#231;&#245;es resumidas limita esta revis&#227;o&#46; Algumas recomenda&#231;&#245;es originaram&#8208;se de dados de ensaios cl&#237;nicos&#44; enquanto outras se basearam em an&#225;lises retrospectivas e pequenas s&#233;ries de casos&#46; As recomenda&#231;&#245;es provavelmente ser&#227;o atualizadas &#224; medida que novos resultados surgirem&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">As terapias direcionadas revolucionaram o tratamento de doen&#231;as cr&#244;nicas da pele&#44; oferecendo novas op&#231;&#245;es para pacientes que n&#227;o respondem aos tratamentos padr&#227;o&#46; Rea&#231;&#245;es paradoxais s&#227;o raramente observadas&#46; Mais estudos s&#227;o necess&#225;rios para compreender completamente os mecanismos e a natureza dessas terapias&#46; Em geral&#44; as terapias imunol&#243;gicas direcionadas em dermatologia representam um desenvolvimento promissor&#44; melhorando significantemente a qualidade de vida dos pacientes com doen&#231;as cr&#244;nicas inflamat&#243;rias da pele&#46;</p></span>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; IV&#44; intravenosa&#59; a&#44; anos&#59; PASI&#44; <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#59; ASC&#44; &#225;rea da superf&#237;cie corporal&#59; DLQI&#44; <span class="elsevierStyleItalic">Dermatology Life Quality Index</span>&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risanquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 150 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 150 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guselcumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 100 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 100 mg a cada 8 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tildraquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 100 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 100 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brodalumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 210 mg semanas 0&#44; 1 e 2&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; BSA ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 210 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixequizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 160 mg semana 0 SC&#44; 80 mg semanas 2&#44; 4&#44; 6&#44; 8&#44; 10&#44; 12&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; BSA ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 80 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secuquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 300 mg semanas 0&#44;1&#44;2&#44;3 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg todos os meses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;12&#47;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustequinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;12&#47;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 45 mg semanas 0 e 4&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 90 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adultos&#58; 42&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 45 mg a cada 12 semanas&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 90 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#44; 40 mg semana 1&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Certolizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 400 mg semanas 0&#44; 2 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>90 kg&#58; 200 mg a cada duas semanas&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>90 kg&#58; 400 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Golimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 200 mg na semana 0&#44; 100 mg na semana 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#37; PASI&#8208;75 semana 14<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">25</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 50 mg mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 50 mg duas vezes por semana&#47;SC durante 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adultos&#58; 23&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 50 mg uma vez por semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK&#8208;2i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deucravacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidor de JAK&#8208;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#37; PASI&#8208;75 semana 16<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;30&#8211;32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para psor&#237;ase</p>"
        ]
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      3 => array:8 [
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        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; IV&#44; intravenosa&#59; EASI&#44; Eczema Area and Severity Index&#59; ASC&#44; &#225;rea de superf&#237;cie corporal&#59; IGA&#44; avalia&#231;&#227;o global do investigador&#59; SCORAD&#44; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis</span>&#44; PP&#8208;NRS&#44; <span class="elsevierStyleItalic">Peak Pruritus Numerical Rating Scale</span>&#59; DA&#44; dermatite at&#243;pica&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upadacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#8208;30 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; EASI&#8208;75 semana 16 &#40;30 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abrocitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;200 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#37; EASI&#8208;75 semana 16 &#40;200 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#37; EASI&#8208;75 semana 16<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">51</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lebriquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 500 mg semanas 0 e 2&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;8&#37; EASI&#8208;75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1065"><span class="elsevierStyleSup">55</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 250 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baricitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#37; EASI&#8208;75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Traloquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37; EASI&#8208;75 semana 16<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">48</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoquimabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300 mg na semana 0&#44; 150 mg nas semanas 4&#44; 8 e 12&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#37; EASI&#8208;75 na semana 4<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">65</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fezaquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;22</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SCORAD decl&#237;nio de 14 pontos na semana 12<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">63</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas durante 10 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nemolizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 69&#37; no EASI na semana 12 &#40;30 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">64</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tezepelumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TSLP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">280 mg a cada duas semanas por tr&#234;s meses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#37; EASI&#8208;50 semana 12<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">62</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#37; uso t&#243;pico&#44; uma vez&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IGA 2&#8208;3&#44; ASC 2&#8208;20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 82&#37; no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">67</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IGA 2&#8208;3&#44; ASC 2&#37;&#8208;20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 71&#37; no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">66</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para dermatite at&#243;pica</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; HiSCR&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Clinical Response</span>&#59; HSSI&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Severity Index</span>&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 160 mg dia 0&#44; 80 mg dia 15&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&#8208;59&#37; melhora na HiSCR em 50&#37; dos pacientes na semana 12<a class="elsevierStyleCrossRef" href="#bib1205"><span class="elsevierStyleSup">83</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg por semana&#47;SC ou 80 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 mg uma vez ao dia&#47;SC por 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37; dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">86</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bermequimabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400 mg cada semana&#47;SC por 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximab</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37;&#8208;50&#37; de melhora no HSSI na semana 8<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "tabla" => array:2 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa&#44; 19&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">91</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8208;50 mg cada semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa&#44; 30&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#37; de resposta completa&#44; 14&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 mg uma vez&#47;dia&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37; de resposta completa&#44; 21&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Canaquinumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&#8208;300 mg a cada 4&#8208;8 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#37; de resposta completa&#44; 9&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustequinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;12&#47;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 90 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; de resposta completa&#44; 8&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 45 mg semanas 4 e 8&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;2 resposta completa ap&#243;s um a 15 meses<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3563625.png"
              ]
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para pioderma gangrenoso</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Tabela 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; UAS7&#44; <span class="elsevierStyleItalic">Urticaria Activity Score</span> por 7 dias seguidos&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omalizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&#8208;300 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#44;3&#37; de resposta completa em 40 semanas<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">100</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Se refrat&#225;ria&#44; considerar 600 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ligelizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#8208;240 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#37; de resposta completa na semana 12<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">102&#44;103</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secuquinumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 150 mg nas semanas 0&#44; 1&#44; 2 e 3&#47;SC Manuten&#231;&#227;o&#58; 150 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria ao omalizumabe &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Redu&#231;&#227;o de 82&#37; no UAS7 na semana 12<a class="elsevierStyleCrossRef" href="#bib1330"><span class="elsevierStyleSup">108</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria ao omalizumabe &#40;no contexto da pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em uma s&#233;rie de casos de seis pacientes<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lirentelimabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;SIGLEC&#8208;8</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose inicial&#58; 0&#44;3 mg&#47;kg no dia 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215; &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#37; de resposta completa em 22 semanas<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">104</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doses subsequentes&#58; 1 mg&#47;kg nos dias 29&#44; 57&#44; 85&#44; 113 e 141&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benralizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;5</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 30 mg a cada quatro semanas por tr&#234;s doses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento em UEC refrat&#225;ria ao antiH1</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#37; de resposta completa em 20 semanas<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 30 mg a cada oito semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;300 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento em UEC refrat&#225;ria ao antiH1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baricitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 mg uma vez&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#37;&#8208;38&#37; de restaura&#231;&#227;o capilar adequada na semana 36<a class="elsevierStyleCrossRef" href="#bib1335"><span class="elsevierStyleSup">109</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#37; de resposta completa e 58&#37; de restaura&#231;&#227;o capilar adequada durante quatro a 18 meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">111</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ritlecitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 mg uma vez&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#37; dos pacientes apresentam &#62;<span class="elsevierStyleHsp" style=""></span>80&#37; de restaura&#231;&#227;o capilar em seis meses<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">112</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#37; de resposta completa e 64&#37; de restaura&#231;&#227;o capilar adequada durante seis meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para alopecia areata</p>"
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      8 => array:8 [
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        "etiqueta" => "Tabela 7"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at7"
            "detalle" => "Tabela "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; PDAI&#44; <span class="elsevierStyleItalic">Pemphigus Disease and Area Index</span>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 g em duas ocasi&#245;es com intervalo de duas semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinado com prednisona&#44; 89&#37; de resposta completa em 24 meses<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efgartigimode&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Receptor antirreceptor Fc neonatal &#40;FcRn&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8208;25 mg semanalmente durante quatro semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinado com prednisona&#44; resposta completa em 64&#37; dos pacientes em 2&#8208;41 semanas<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">118</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ianalumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;BLyS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 mg&#47;kg IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 73&#37; no escore m&#233;dio de PDAI na semana 12<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">120</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">375 mg&#47;m<span class="elsevierStyleSup">2</span> a cada 1&#8208;4 semanas at&#233; 500 mg semanalmente por duas semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;5&#37; de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omalizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;525 mg a cada uma a quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; dose &#250;nica de 600 mg&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;7&#37; de resposta completa em 4&#44;5 meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "pt" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para doen&#231;as bolhosas</p>"
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          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; RC&#44; resposta completa&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SSJ&#47;NET</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>65 kg&#58; 25 mg dias 0 e 3&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Em uso no contexto de pesquisa</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortalidade de 7&#44;6&#37;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>65 kg&#58; 50 mg dias 0 e 3&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg&#47;kg dose &#250;nica&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Em uso no contexto de pesquisa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortalidade de 22&#37;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#47;SC&#44; 40 mg semana 1&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#170; linha em LP mucoso&#44; 3&#170; linha em LP cut&#226;neo</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora no prurido e na cicatriza&#231;&#227;o de les&#245;es cut&#226;neas durante um per&#237;odo de seis meses<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">133</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada duas semanas SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes ao dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano cut&#226;neo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 7&#44;6 pontos de mCAILS em quatro semanas<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano pilar e l&#237;quen plano hipertr&#243;fico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 46&#37; no LPPAI em 12 semanas no l&#237;quen plano pilar<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">145</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#250;pus Eritematoso Cut&#226;neo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anifrolumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IFN&#8208;&#947;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300 mg&#47;IV a cada quatro semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sintomas cut&#226;neos no contexto de l&#250;pus eritematoso sist&#234;mico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#37; dos pacientes alcan&#231;aram redu&#231;&#227;o no escore CLASI &#8805; 50&#37;<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">140</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes ao dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 75&#37; no VASI em 30&#37; dos pacientes na semana 24<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">141</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidor de JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#37; t&#243;pico duas vezes&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 70&#37; no VASI em quatro meses &#40;&#225;reas expostas ao sol&#41;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 5&#44;4&#37; na ASC em 50&#37; dos pacientes<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">143</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Granuloma anular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;rio &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sarcoidose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em s&#233;ries de casos<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DiHS&#47;DRESS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRefs" href="#bib1445"><span class="elsevierStyleSup">131&#44;132</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 mg dose &#250;nica &#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primeira linha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRefs" href="#bib1445"><span class="elsevierStyleSup">131&#44;132</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;ndrome hipereosinof&#237;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 mg de manh&#227;&#8208;10 mg &#224; noite&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">137</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morfeia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em relato de caso<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">149</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Artigo Original
Terapia direcionada para doenças imunomediadas da pele. O que o dermatologista deve saber?
Edinson López, Raúl Cabrera
Corresponding author
rcabrera237@gmail.com

Autor para correspondência.
, Cristóbal Lecaros
Departamento de Dermatologia, Faculdade de Medicina, Universidad del Desarrollo‐Clínica Alemana de Santiago, Santiago, Chile
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">As terapias de alvo molecular tornaram&#8208;se ferramenta importante para o tratamento de doen&#231;as dermatol&#243;gicas&#46;<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Os principais grupos de terapia direcionada para doen&#231;as inflamat&#243;rias da pele s&#227;o os anticorpos monoclonais &#40;mAbs&#41; e os inibidores da Janus Quinase &#40;JAKis&#41;&#44; mas tamb&#233;m existem prote&#237;nas de fus&#227;o produzidas por DNA recombinante&#44; como o etanercepte&#46; Anteriormente chamados de produtos biol&#243;gicos&#44; uma vez que eram sintetizados como produtos de organismos vivos&#44; atualmente essas terapias tamb&#233;m s&#227;o compostas de pequenas mol&#233;culas &#8211; portanto&#44; os termos terapia direcionada ou terapia&#8208;alvo devem ser preferidos&#46;<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">2</span></a> Al&#233;m disso&#44; o termo moduladores imunol&#243;gicos direcionados &#233; utilizado em livros de refer&#234;ncia&#46;<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O mecanismo de a&#231;&#227;o &#233; heterog&#234;neo entre as diferentes mol&#233;culas&#44; mas todas elas modulam o sistema imunol&#243;gico por meio de impulsos estimulat&#243;rios ou inibit&#243;rios&#44; atuando em pontos espec&#237;ficos das vias de sinaliza&#231;&#227;o da inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">4</span></a> Sua efic&#225;cia e perfil de seguran&#231;a s&#227;o frequentemente hom&#243;logos aos agentes imunossupressores sist&#234;micos padr&#227;o ou at&#233; melhores&#46; Como todos os novos medicamentos&#44; eles n&#227;o est&#227;o isentos de eventos adversos &#40;EA&#41; e seu custo representa barreira importante para sua acessibilidade&#46;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Os primeiros exemplos de terapias imunol&#243;gicas direcionadas para doen&#231;as inflamat&#243;rias em dermatologia foram os ensaios cl&#237;nicos de alefacepte&#44;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">6</span></a> efalizumabe&#44;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">7</span></a> etanercepte<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">8</span></a> e infliximabe<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">9</span></a> para psor&#237;ase no in&#237;cio dos anos 2000&#46; Alefacepte e efalizumabe foram substitu&#237;dos por mol&#233;culas mais novas com renova&#231;&#227;o constante dos medicamentos utilizados em terapias imunol&#243;gicas direcionadas para diferentes doen&#231;as inflamat&#243;rias da pele &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Esta revis&#227;o narrativa tem como objetivo atualizar&#44; resumir e priorizar a grande quantidade de informa&#231;&#245;es sobre importantes doen&#231;as inflamat&#243;rias cut&#226;neas em formato pr&#225;tico para uso na cl&#237;nica&#46; Indica&#231;&#245;es de uso s&#227;o sugeridas considerando dados atuais sobre efic&#225;cia&#44; dose e perfil de seguran&#231;a da imunoterapia direcionada&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Material e m&#233;todos</span><p id="par0030" class="elsevierStylePara elsevierViewall">Esta revis&#227;o foi realizada com base nas diretrizes <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews and Meta&#8208;analyses</span> &#40;PRISMA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">10</span></a> Foi feita pesquisa sistem&#225;tica no banco de dados Pubmed nos &#250;ltimos 10 anos &#40;janeiro de 2012 a julho de 2023&#59; estrat&#233;gia de busca&#44; ver Material Suplementar 1&#41;&#46; As refer&#234;ncias de todos os estudos inclu&#237;dos tamb&#233;m foram avaliadas para identificar quaisquer estudos eleg&#237;veis adicionais&#46; Foram selecionadas revis&#245;es sistem&#225;ticas e ensaios cl&#237;nicos randomizados &#40;RCE&#44; em ingl&#234;s&#41;&#46; Tamb&#233;m foram inclu&#237;dos relatos de casos e s&#233;ries de casos&#44; se realizados em humanos&#46; Os estudos foram exclu&#237;dos se o produto biol&#243;gico utilizado estivesse no contexto da medicina alternativa ou se a qualidade do relato fosse considerada insuficiente&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Extra&#231;&#227;o de dados</span><p id="par0035" class="elsevierStylePara elsevierViewall">Os t&#237;tulos e resumos de todos os artigos foram selecionados de maneira independente para elegibilidade por dois autores &#40;E&#46;L&#46; e C&#46;L&#46;&#41;&#46; Os textos completos dos artigos considerados potencialmente eleg&#237;veis foram avaliados criticamente e avaliados quanto &#224; elegibilidade&#46; Qualquer desacordo sobre a inclus&#227;o ou exclus&#227;o de um artigo entre os dois investigadores foi analisado por um terceiro investigador &#40;RC&#41; para chegar a um consenso&#46; Os dados extra&#237;dos de cada estudo inclu&#237;ram dados de cita&#231;&#227;o &#40;t&#237;tulo do estudo&#44; autores&#44; ano de publica&#231;&#227;o&#41;&#44; desenho do estudo &#40;objetivo do estudo&#44; per&#237;odo&#44; cen&#225;rio&#41; e resultados &#40;demografia da popula&#231;&#227;o&#44; medidas de desfecho&#41;&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Busca na literatura</span><p id="par0040" class="elsevierStylePara elsevierViewall">Foram identificados 1&#46;360 artigos n&#227;o duplicados com a estrat&#233;gia de busca inicial&#46; A revis&#227;o do t&#237;tulo e do resumo excluiu 1&#46;150&#44; enquanto a revis&#227;o do texto completo excluiu 50 artigos adicionais&#46; Foram inclu&#237;dos 143 estudos nesta revis&#227;o&#44; como descrito no fluxograma PRISMA &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Psor&#237;ase</span><p id="par0045" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a cut&#226;nea cr&#244;nica imunomediada que afeta aproximadamente 1&#37; da popula&#231;&#227;o mundial&#46;<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">11&#8211;13</span></a> Apesar de evid&#234;ncias convincentes que apoiam o uso de terapias imunol&#243;gicas direcionadas&#44; a sele&#231;&#227;o de medicamento espec&#237;fico pode ser desafiadora&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">14</span></a> A decis&#227;o final do tratamento deve incluir a prefer&#234;ncia do paciente e&#44; eventualmente&#44; a consulta com m&#233;dicos de outras especialidades para equilibrar riscos e benef&#237;cios&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Crit&#233;rios de eligibilidade</span><p id="par0050" class="elsevierStylePara elsevierViewall">Os pacientes devem ser considerados para terapia imunol&#243;gica direcionada em diversas circunst&#226;ncias&#58; se houver psor&#237;ase grave&#44;<a class="elsevierStyleCrossRefs" href="#bib0865"><span class="elsevierStyleSup">15&#8211;17</span></a> definida como envolvimento superior a 10&#37; da &#225;rea de superf&#237;cie corporal &#40;ASC&#41; total&#44; escore PASI &#40;<span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#41; ou DLQI &#40;<span class="elsevierStyleItalic">Dermatology Life Quality Index</span>&#41; &#62;<span class="elsevierStyleHsp" style=""></span>10 ou comprometimento de locais espec&#237;ficos &#40;m&#227;os&#44; p&#233;s&#44; couro cabeludo&#44; rosto ou &#225;rea genital&#41;&#59; quando a psor&#237;ase causa prurido n&#227;o trat&#225;vel ou tem consequ&#234;ncias emocionais graves com dura&#231;&#227;o da doen&#231;a superior a seis meses&#44;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">15</span></a> ou n&#227;o responde &#224; terapia convencional&#44; ou n&#227;o pode receber terapia sist&#234;mica padr&#227;o em virtude do estado geral do paciente e de comorbidades ou quando o paciente tem doen&#231;a grave&#44; como psor&#237;ase eritrod&#233;rmica&#44; pustulosa ou artrite psori&#225;sica&#46;<a class="elsevierStyleCrossRefs" href="#bib0865"><span class="elsevierStyleSup">15&#8211;17</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Terapia</span><p id="par0055" class="elsevierStylePara elsevierViewall">Existem m&#250;ltiplas imunoterapias direcionadas para a psor&#237;ase&#46; Terapias direcionadas como anti&#8208;TNF&#8208;&#945;&#44; anti&#8208;IL&#8208;17&#44; anti&#8208;IL&#8208;23 e anti&#8208;IL&#8208;12&#47;23 podem atingir PASI&#8208;90 em mais pacientes do que o tratamento sist&#234;mico anterior &#40;p&#46; ex&#46;&#44; ciclosporina e metotrexato&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a> Os tratamentos anti&#8208;IL&#8208;17 &#40;ou seja&#44; ixequizumabe&#44; secuquinumabe e brodalumabe&#41; e anti&#8208;IL&#8208;23 &#40;risanquizumabe&#44; tildrakizumabe e guselcumabe&#41; mostraram propor&#231;&#227;o maior de pacientes que alcan&#231;aram PASI&#8208;90 em compara&#231;&#227;o com todas as interven&#231;&#245;es sist&#234;micas avaliadas na &#250;ltima metan&#225;lise de rede&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Os inibidores de TNF&#8208;&#945; foram os primeiros medicamentos biol&#243;gicos aprovados para o tratamento da psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">12&#44;19</span></a> A metan&#225;lise mostra que&#44; nessa classe&#44; o infliximabe tem a maior efic&#225;cia&#44; seguido pelo certolizumabe&#44; adalimumabe e etanercepte&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;19</span></a> A FDA aprovou sequencialmente o etanercepte &#40;2004&#41;&#44; infliximabe &#40;2005&#41;&#44; adalimumabe &#40;2008&#41;&#44; golimumabe &#40;2017&#41; e certolizumabe &#40;2018&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Os inibidores da IL&#8208;17 atingem elimina&#231;&#227;o total da doen&#231;a &#40;isto &#233;&#44; PASI&#8208;100&#41; em cerca de metade dos pacientes<a class="elsevierStyleCrossRefs" href="#bib0845"><span class="elsevierStyleSup">11&#44;12</span></a> e t&#234;m in&#237;cio de a&#231;&#227;o mais r&#225;pido&#46; Os medicamentos aprovados pela FDA para tratar a psor&#237;ase s&#227;o secuquinumabe &#40;2015&#41;&#44; ixekizumabe &#40;2016&#41; e brodalumabe &#40;2017&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Os inibidores de IL&#8208;23&#44; risanquizumabe e guselcumabe&#44; demonstraram recentemente melhor perfil de efic&#225;cia e seguran&#231;a em compara&#231;&#227;o com o anti&#8208;IL&#8208;17 e regime de dosagem conveniente&#46;<a class="elsevierStyleCrossRefs" href="#bib0890"><span class="elsevierStyleSup">20&#44;21</span></a> Os medicamentos aprovados pela FDA s&#227;o guselcumabe &#40;2017&#41;&#44; tildraquizumabe &#40;2018&#41; e risanquizumabe &#40;2019&#41;&#46; Ustequinumabe &#40;2013&#41; &#233; um mAb que inibe IL&#8208;12 e IL&#8208;23&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">JAKis &#40;deucravacitinibe&#44; peficitinibe&#44; baricitinibe&#44; solcitinibe&#44; itacitinibe&#44; abrocitinibe&#44; brepocitinibe&#44; ruxolitinibe e tofacitinibe&#41; tamb&#233;m t&#234;m sido utilizados para o tratamento de pacientes psori&#225;sicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0900"><span class="elsevierStyleSup">22&#44;23</span></a> Embora ainda n&#227;o haja dados completos sobre o impacto cl&#237;nico final no tratamento da psor&#237;ase&#44; ensaios recentes mostram resposta melhor do que certas terapias convencionais &#40;p&#46; ex&#46;&#44; metotrexato&#44; ciclosporina&#41;&#44; mas inferior &#224; terapia imunol&#243;gica direcionada &#40;p&#46; ex&#46;&#44; risanquizumabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">18</span></a> O deucravacitinibe<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">24&#44;25</span></a>&#44; um inibidor alost&#233;rico seletivo da tirosina quinase 2 &#40;TYK2&#41;&#44; &#233; o &#250;nico JAKi aprovado pela FDA &#40;2022&#41;&#44; alcan&#231;ando PASI&#8208;75 de 70&#37; na semana 24&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Nos &#250;ltimos anos &#40;2004&#8208;2020&#41; foram publicadas 51 diretrizes cl&#237;nicas abordando o tratamento da psor&#237;ase&#44; e 41 delas mencionam o uso de produtos biol&#243;gicos&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">26</span></a> Durante o per&#237;odo de 2021&#8208;2022&#44; v&#225;rias sociedades dermatol&#243;gicas atualizaram suas diretrizes cl&#237;nicas considerando a aprova&#231;&#227;o de novas mol&#233;culas pelas ag&#234;ncias reguladoras de medicamentos&#46;<a class="elsevierStyleCrossRefs" href="#bib0925"><span class="elsevierStyleSup">27&#8211;33</span></a> As diretrizes reconhecem medicamentos anti&#8208;IL&#8208;23 e anti&#8208;IL&#8208;17 como parte dos tratamentos de primeira linha para o manejo da psor&#237;ase&#46; H&#225; grande preocupa&#231;&#227;o em rela&#231;&#227;o a seu alto custo e acessibilidade&#46; A decis&#227;o final para a sele&#231;&#227;o de um medicamento para o tratamento do paciente psori&#225;sico depende de diversos fatores cl&#237;nicos e epidemiol&#243;gicos &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Perfil de seguran&#231;a da imunoterapia direcionada para psor&#237;ase</span><p id="par0085" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a da imunoterapia direcionada para psor&#237;ase est&#225; bem descrito&#59; os EA mais comuns s&#227;o as infec&#231;&#245;es do trato respirat&#243;rio superior e rea&#231;&#245;es no local da inje&#231;&#227;o para todas as classes de medicamentos&#46;<a class="elsevierStyleCrossRefs" href="#bib0960"><span class="elsevierStyleSup">34&#44;35</span></a> Considera&#231;&#245;es gerais devem ser tomadas em rela&#231;&#227;o &#224; reativa&#231;&#227;o de tuberculose e hepatites B e C&#46; O uso de JAKis tamb&#233;m deve considerar infec&#231;&#245;es anteriores por membros da fam&#237;lia Herpesv&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">As evid&#234;ncias atuais mostram que a imunoterapia direcionada n&#227;o aumenta o risco de EA cardiovasculares importantes&#44; como infarto do mioc&#225;rdio&#44; acidente vascular encef&#225;lico ou morte cardiovascular ou a incid&#234;ncia de neoplasias malignas&#46;<a class="elsevierStyleCrossRefs" href="#bib0965"><span class="elsevierStyleSup">35&#44;37&#8211;39</span></a>Rea&#231;&#227;o adversa cut&#226;nea comum &#233; a mudan&#231;a fenot&#237;pica de psor&#237;ase para eczema at&#243;pico&#44; que ocorre em at&#233; 1&#37;&#8208;12&#44;1&#37; dos pacientes que tomam medicamentos anti&#8208;TNF&#8208;&#945; ou anti&#8208;IL&#8208;17&#47;IL&#8208;23&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">40</span></a> O tratamento t&#243;pico foi bem&#8208;sucedido em alguns casos&#44; mas em outros o tratamento biol&#243;gico precisa ser interrompido&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Rea&#231;&#227;o paradoxal &#8211; piora da psor&#237;ase e&#47;ou novas les&#245;es psori&#225;sicas &#8211; foi relatada com o uso de certos medicamentos &#40;p&#46; ex&#46;&#44; medicamentos anti&#8208;TNF&#8208;&#945; e ustequinumabe&#41;&#46; Essas rea&#231;&#245;es geralmente n&#227;o exigem a interrup&#231;&#227;o da terapia e s&#227;o autolimitadas&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">37</span></a> Outras rea&#231;&#245;es adversas relevantes com a classe anti&#8208;TNF&#8208;&#945; s&#227;o infec&#231;&#227;o do trato urin&#225;rio&#44; dor nas costas&#44; artralgia&#44; prurido e erisipela&#44; e infec&#231;&#245;es f&#250;ngicas invasivas&#44; linfoma&#44; insufici&#234;ncia card&#237;aca&#44; citopenia&#44; indu&#231;&#227;o ou exacerba&#231;&#227;o de doen&#231;a desmielinizante e s&#237;ndrome semelhante a l&#250;pus &#40;p&#46; ex&#46;&#44; infliximabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">40</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Os medicamentos anti&#8208;IL&#8208;17 e anti&#8208;IL&#8208;12&#47;23 t&#234;m menos dados sobre seu perfil de seguran&#231;a&#46; Uma rea&#231;&#227;o adversa de interesse nos inibidores de IL&#8208;17 e IL&#8208;12&#47;23 &#233; a candid&#237;ase mucocut&#226;nea &#40;1&#44;7&#37; em pacientes tratados com secuquinumabe&#44; 3&#44;3&#37; com ixequizumabe&#44; 4&#44;0&#37; com brodalumabe e 2&#44;3&#37; de ustequinumabe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">41</span></a> Epis&#243;dios de exacerba&#231;&#227;o de doen&#231;a inflamat&#243;ria intestinal tamb&#233;m foram observados com o uso desses medicamentos&#46; Pacientes com hist&#243;ria de doen&#231;a de Crohn ou colite ulcerativa devem ser tratados com outra imunoterapia direcionada&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">37</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Para os JAKis&#44; os EA mais comuns foram reativa&#231;&#227;o de herpes simples&#44; &#250;lceras bucais&#44; pneumonia&#44; COVID&#8208;19&#44; neoplasias malignas&#44; incluindo linfoma&#44; rabdomi&#243;lise&#44; aumento da creatina fosfoquinase&#44; aumento dos triglicer&#237;deos e aumento das transaminases&#46;<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">23</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Com os dados dispon&#237;veis&#44; as taxas de qualquer EA foram as mais baixas para tildraquizumabe&#44; certolizumabe e etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">34</span></a> Para EA graves&#44; os mais baixos foram para certolizumabe&#44; risanquizumabe e etanercepte&#46; No tratamento de longo prazo&#44; o risanquizumabe apresentou o perfil de risco&#8208;benef&#237;cio mais favor&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Popula&#231;&#245;es especiais</span><p id="par0115" class="elsevierStylePara elsevierViewall">Gr&#225;vidas&#58; o &#250;nico mAb aprovado pela FDA para uso em pacientes gr&#225;vidas &#233; o certolizumabe pegol&#46; &#201; um fragmento peguilado da por&#231;&#227;o Fab dirigido contra o TNF&#8208;&#945; que n&#227;o atravessa a membrana placent&#225;ria&#46;<a class="elsevierStyleCrossRefs" href="#bib0850"><span class="elsevierStyleSup">12&#44;19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Pedi&#225;trica&#58; Os mAbs autorizados pela FDA para crian&#231;as &#62;<span class="elsevierStyleHsp" style=""></span>4 anos s&#227;o etanercepte e adalimumabe&#44; secuquinumabe a partir dos 6 anos e ustequinumabe a partir dos 12 anos&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;19&#44;42</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Dermatite at&#243;pica</span><p id="par0125" class="elsevierStylePara elsevierViewall">A dermatite at&#243;pica &#40;DA&#41; &#233; doen&#231;a inflamat&#243;ria cut&#226;nea cr&#244;nica e recidivante que afeta 2&#37;&#8208;5&#37; dos adultos e 20&#37; das crian&#231;as&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">43</span></a> A efic&#225;cia da terapia imunol&#243;gica direcionada na DA foi comprovada por v&#225;rios estudos&#46; Uma revis&#227;o sistem&#225;tica recente de 60 ensaios cl&#237;nicos realizados em 16&#46;579 pacientes confirma a efic&#225;cia cl&#237;nica dessas terapias direcionadas na DA&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Crit&#233;rios de elegibilidade</span><p id="par0130" class="elsevierStylePara elsevierViewall">Tanto crian&#231;as quanto adultos podem ser considerados para receber terapia imunol&#243;gica direcionada se tiverem doen&#231;a grave&#44; definida como envolvimento de mais de 10&#37; da ASC total&#44; Avalia&#231;&#227;o Global do Investigador &#40;IGA&#41; de pelo menos 3&#44; escore EASI &#40;<span class="elsevierStyleItalic">Eczema Area and Severity Index</span>&#41; &#8805; 16&#44; escore SCORAD &#40;<span class="elsevierStyleItalic">Scoring Atopic Dermatitis</span>&#41; &#8805; 50 e escore de gravidade da <span class="elsevierStyleItalic">Pruritus Numerical Rating Scale</span> &#40;PP&#8208;NRS&#41; &#8805; 4&#44; ou quando o prurido &#233; intrat&#225;vel ou tem consequ&#234;ncias emocionais graves&#46;<a class="elsevierStyleCrossRefs" href="#bib1015"><span class="elsevierStyleSup">45&#44;46</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Terapia</span><p id="par0135" class="elsevierStylePara elsevierViewall">Est&#227;o dispon&#237;veis m&#250;ltiplas terapias direcionadas para a DA que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; O dupilumabe demonstrou efic&#225;cia semelhante &#224; ciclosporina em doses mais altas em pacientes com mais de 6 meses de idade&#44; com resposta mais confi&#225;vel e superioridade ao metotrexato e &#224; azatioprina&#44; e consideravelmente menos efeitos adversos&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Isso tornou a terapia imunol&#243;gica direcionada muito promissora na DA&#44; mas a compara&#231;&#227;o da efic&#225;cia e seguran&#231;a entre as terapias direcionadas &#233; dif&#237;cil&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;47</span></a> Quatro medicamentos sist&#234;micos foram aprovados pela FDA &#40;dupilumabe&#44;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">48</span></a> traloquinumabe&#44;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">49</span></a> abrocitinibe<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">50</span></a> e upadacitinibe<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">51</span></a>&#41; e outros medicamentos est&#227;o sendo usados <span class="elsevierStyleItalic">off&#8208;label</span> ou em ensaios cl&#237;nicos&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">Em compara&#231;&#227;o com dupilumabe&#44; o abrocitinibe&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; e upadacitinibe&#44; 30<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; foram associados a redu&#231;&#245;es mais altas nos escores EASI&#44; enquanto com baricitinibe e traloquinumabe&#44; as redu&#231;&#245;es nos escores EASI foram semelhantes ou ligeiramente piores do que com dupilumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Dupilumabe &#233; mAb anti&#8208;IL&#8208;4&#47;13 aprovado pela FDA em 2017 para o tratamento de DA moderada a grave&#44; a partir dos 6 meses de idade&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">52</span></a> O efeito terap&#234;utico do dupilumabe &#233; mediado principalmente pela inibi&#231;&#227;o da subunidade alfa do receptor da IL&#8208;4 &#40;IL&#8208;4R&#945;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1055"><span class="elsevierStyleSup">53&#44;54</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Traloquinumabe &#233; mAb anti&#8208;IL&#8208;13 aprovado pela FDA em 2021 para o tratamento de DA moderada a grave em adultos&#46; Em dois ECRs&#44; 300<span class="elsevierStyleHsp" style=""></span>mg de traloquinumabe a cada duas semanas alcan&#231;ou escore EASI&#8208;75 em 25&#37;&#8208;33&#44;2&#37; dos pacientes em 16 semanas de tratamento&#46; Esses ECRs tamb&#233;m mostraram melhoras precoces no prurido&#44; interfer&#234;ncia no sono e escore DLQI&#46; Os pacientes mantiveram essas respostas ap&#243;s 52 semanas de tratamento com traloquinumabe sem qualquer medica&#231;&#227;o de resgate&#46;<a class="elsevierStyleCrossRefs" href="#bib1035"><span class="elsevierStyleSup">49&#44;55</span></a> Lebriquizumabe&#44; mAb que tem como alvo a IL&#8208;13 foi avaliado em dois ensaios de fase 3 randomizados&#44; duplo&#8208;cegos&#44; controlados por placebo&#44; em pacientes maiores de 12 anos com DA moderada a grave mostrando escore EASI&#8208;75 em 58&#44;8&#37; e 52&#44;1&#37; dos pacientes&#44; respectivamente&#44; na semana 16&#46;<a class="elsevierStyleCrossRef" href="#bib1070"><span class="elsevierStyleSup">56</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">O abrocitinibe &#233; inibidor de JAK&#8208;1 aprovado pela FDA em 2022 para o tratamento de DA em adultos&#46; Na DA moderada a grave&#44; o abrocitinibe mostrou respostas consistentes no tratamento e n&#227;o apresentou novas preocupa&#231;&#245;es de seguran&#231;a em compara&#231;&#227;o com o dupilumabe&#46;<a class="elsevierStyleCrossRefs" href="#bib1020"><span class="elsevierStyleSup">46&#44;57&#8211;59</span></a> Ele &#233; utilizado na dose de 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; atingindo 70&#37; do escore EASI&#8208;75 na semana 12 de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">58</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Upadacitinibe &#233; um inibidor de JAK&#8208;1 aprovado pela FDA &#40;2022&#41; para o tratamento de DA em pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos&#46; Ele mostra uma melhora no escore EASI&#8208;75 de 71&#37; na semana 16 com uma dose de 30<span class="elsevierStyleHsp" style=""></span>mg&#47;dia por via oral&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">60</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Recentemente&#44; o baricitinibe&#44; um inibidor de primeira gera&#231;&#227;o de JAK 1&#8208;2 ainda n&#227;o aprovado pela FDA na DA&#44; completou ECR de fase 2 e 3 em combina&#231;&#227;o com corticosteroides t&#243;picos em adultos com DA moderada a grave&#46; Na semana 16&#44; o baricitinibe 4<span class="elsevierStyleHsp" style=""></span>mg proporcionou melhora de 54&#44;9&#37; e 59&#44;4&#37; no escore EASI no BREEZE&#8208;AD1 e BREEZE&#8208;AD2&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">61</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Tezepelumabe &#233; mAb humano que se liga &#224; linfopoietina estromal do timo &#40;TSLP&#44; citocina derivada de c&#233;lulas epiteliais que induz a produ&#231;&#227;o de citocinas Th2&#44; incluindo IL&#8208;4&#44; IL&#8208;5 e IL&#8208;13&#41;<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">62</span></a> usado no tratamento da asma&#46; Ele foi testado em doses de 280<span class="elsevierStyleHsp" style=""></span>mg a cada duas semanas em estudos de fase 2&#44; alcan&#231;ando escore EASI&#8208;50 em 65&#37; dos pacientes na 12&#170; semana de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">63</span></a> Fezaquinumabe&#44; mAb humano contra IL&#8208;22&#44; est&#225; em estudos de fase 2&#46; Doses de indu&#231;&#227;o de 600<span class="elsevierStyleHsp" style=""></span>mg seguidas de 300<span class="elsevierStyleHsp" style=""></span>mg a cada duas semanas demonstraram melhora no escore IGA a partir de 12 semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">64</span></a> Nemolizumabe &#233; mAb anti&#8208;IL&#8208;31RA experimentado em estudos de fase 2&#46; Foi relatado que 42&#37; dos pacientes tratados apresentaram melhora no escore EASI ap&#243;s 12 semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">65</span></a> O etoquimabe &#233; outro mAb experimental que se liga &#224; IL&#8208;33 em fase inicial de desenvolvimento&#46; No momento&#44; os estudos testaram doses de 300<span class="elsevierStyleHsp" style=""></span>mg IV uma vez&#44; alcan&#231;ando escore EASI&#8208;50 em 100&#37; dos participantes em 140 dias&#46;<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">66</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Novas terapias imunol&#243;gicas t&#243;picas direcionadas para DA apareceram recentemente como ferramentas terap&#234;uticas&#46; O creme de ruxolitinibe 1&#44;5&#37; &#40;aprovado pela FDA em 2021&#41; para pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos mostra melhora de 71&#44;6&#37; no escore EASI ap&#243;s quatro semanas de uso&#46;<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">67</span></a> O creme de tofacitinibe 2&#37; mostrou melhora de 82&#37; no escore EASI ap&#243;s quatro semanas de uso e est&#225; aguardando a aprova&#231;&#227;o da FDA&#46;<a class="elsevierStyleCrossRefs" href="#bib1130"><span class="elsevierStyleSup">68&#44;69</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Perfil de seguran&#231;a da imunoterapia direcionada para DA</span><p id="par0180" class="elsevierStylePara elsevierViewall">Os EA mais comuns foram infec&#231;&#245;es do trato respirat&#243;rio superior e rea&#231;&#245;es no local da inje&#231;&#227;o para todas as classes&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;45</span></a> Considera&#231;&#245;es gerais devem ser observadas em rela&#231;&#227;o &#224; reativa&#231;&#227;o de tuberculose&#44; hepatite B e&#44; no caso de JAKis&#44; considerar tamb&#233;m infec&#231;&#245;es por membros da fam&#237;lia Herpesv&#237;rus&#46;<a class="elsevierStyleCrossRefs" href="#bib1080"><span class="elsevierStyleSup">58&#44;60</span></a> Outros EA comuns em todas as classes foram sintomas oculares &#40;conjuntivite&#44; ceratite&#44; blefarite&#44; prurido ocular&#44; ressecamento e desconforto ocular&#41;&#46; Dupilumabe e traloquinumabe n&#227;o requerem monitoramento laboratorial&#44; mas abrocitinibe&#44; baricitinibe e upadacitinibe necessitam de seguimento laboratorial&#46; Eles podem induzir eleva&#231;&#227;o da creatinofosfoquinase&#44; trombocitopenia e neutropenia&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">45</span></a> Outros EA relatados para JAKis s&#227;o n&#225;usea&#44; cefaleia&#44; diarreia&#44; fadiga&#44; acne&#44; dor abdominal e mialgias&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">70</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Recentemente&#44; observou&#8208;se risco aumentado de artrite inflamat&#243;ria soronegativa e psor&#237;ase em pacientes em uso de dupilumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">71</span></a> Com base nas evid&#234;ncias atuais&#44; parece que o uso de anti&#8208;TNF&#8208;&#945; para psor&#237;ase e anti&#8208;IL&#8208;4&#47;13 para DA est&#227;o inversamente relacionados&#46; O bloqueio duplo com dupilumabe est&#225; associado a doen&#231;as psoriasiformes&#44; enquanto medicamentos biol&#243;gicos para psor&#237;ase podem causar mudan&#231;a fenot&#237;pica para eczema&#46;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">72</span></a></p><p id="par0500" class="elsevierStylePara elsevierViewall">Para produtos t&#243;picos&#44; irrita&#231;&#227;o local leve foi o EA mais comum&#46;<a class="elsevierStyleCrossRefs" href="#bib1125"><span class="elsevierStyleSup">67&#44;68</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">N&#227;o existem dados suficientes para determinar se qualquer terapia imunol&#243;gica direcionada &#233; mais segura do que outra para a DA&#46; O abrocitinibe&#44; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; foi associado a 2&#44;6 vezes mais chances de EA graves em compara&#231;&#227;o com dupilumabe&#44; mas com doses mais altas &#40;isto &#233;&#44; abrocitinibe&#44; 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#41; as chances foram menores &#40;1&#44;4&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Taxas mais baixas de EA graves foram observadas com dupilumabe em compara&#231;&#227;o com placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Dupilumabe tamb&#233;m est&#225; associado a aumento n&#227;o significante na infec&#231;&#227;o por herpes&#46; A raz&#227;o para a diminui&#231;&#227;o de infec&#231;&#245;es cut&#226;neas&#44; incluindo eczema herp&#233;tico&#44; &#233; desconhecida&#44; mas a melhora na barreira cut&#226;nea e no microbioma causada pela imunoterapia direcionada pode explicar essa observa&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1155"><span class="elsevierStyleSup">73</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Hidradenite supurativa</span><p id="par0200" class="elsevierStylePara elsevierViewall">A hidradenite supurativa &#40;HS&#41; &#233; doen&#231;a autoinflamat&#243;ria do fol&#237;culo pilosseb&#225;ceo com preval&#234;ncia variando de 0&#44;05&#37;&#8208;4&#44;1&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a> Existem pelo menos nove diretrizes cl&#237;nicas que consideram o uso de produtos biol&#243;gicos no manejo da HS&#46;<a class="elsevierStyleCrossRefs" href="#bib1165"><span class="elsevierStyleSup">75&#8211;83</span></a></p><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Crit&#233;rios de eligibilidade</span><p id="par0205" class="elsevierStylePara elsevierViewall">O manejo com imunoterapia direcionada deve ser considerado precocemente em casos graves&#46; As diretrizes internacionais recomendam iniciar tratamento direcionado para HS recalcitrante moderada a grave&#44; definida como est&#225;gio II&#8208;III de Hurley&#44; ou contagem total de abcessos e n&#243;dulos inflamat&#243;rios &#8805; 3 no in&#237;cio do estudo e resposta inadequada ao tratamento com antibi&#243;ticos orais por pelo menos 90 dias&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Terapia</span><p id="par0210" class="elsevierStylePara elsevierViewall">Existem poucas terapias direcionadas para HS que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; O adalimumabe<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a> &#233; o &#250;nico tratamento biol&#243;gico aprovado pela FDA para HS &#40;2015&#41; e &#233; recomendado como medicamento biol&#243;gico de primeira linha em todas as diretrizes&#59; o infliximabe &#233; a segunda op&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a> Anakinra e bermequimabe podem ser considerados ap&#243;s falha dos agentes anti&#8208;TNF&#8208;&#945;&#44; mas as evid&#234;ncias que apoiam sua efic&#225;cia na HS s&#227;o limitadas&#46;<a class="elsevierStyleCrossRef" href="#bib1160"><span class="elsevierStyleSup">74</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">O adalimumabe mostrou melhora de 41&#44;8&#37; a 58&#44;9&#37; na resposta cl&#237;nica &#224; HS &#40;HiSCR&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Clinical Response</span>&#41; em 50&#37; dos pacientes em 12 semanas&#46;<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a> O infliximabe demonstrou melhora de 25&#37;&#8208;50&#37; no <span class="elsevierStyleItalic">Hidradenitis Suppurativa Severity Index</span> &#40;HSSI&#41; em 60&#37; dos pacientes em oito semanas&#46;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">85</span></a> Outros anti&#8208;TNFs n&#227;o s&#227;o utilizados para tratar a HS&#44; como etanercepte ou golimumabe&#44; em virtude de rea&#231;&#245;es paradoxais de piora ou indu&#231;&#227;o da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib1160"><span class="elsevierStyleSup">74&#44;86</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Os medicamentos anti&#8208;IL&#8208;1 comprovaram sua efic&#225;cia em pequenos ECR controlados por placebo&#46;<a class="elsevierStyleCrossRefs" href="#bib1225"><span class="elsevierStyleSup">87&#44;88</span></a> Anakinra mostrou melhora &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; no <span class="elsevierStyleItalic">Disease Activity Score</span> &#40;DAS&#41; em 78&#37; dos pacientes em 12 semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">87</span></a> O bermequimabe mostrou melhora de 60&#37; no HiSCR em 12 semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">88</span></a> Esses medicamentos devem ser considerados quando os pacientes n&#227;o s&#227;o candidatos &#224; terapia anti&#8208;TNF&#8208;&#945;&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">As diretrizes cl&#237;nicas tamb&#233;m mencionam outros produtos biol&#243;gicos que t&#234;m sido utilizados com sucesso em s&#233;ries de casos para o tratamento da HS &#40;guselcumabe&#44; risanquizumabe&#44; secuquinumabe&#44; bimequizumabe e upadacitinibe&#41;&#44; mas os resultados em pacientes tratados com esses medicamentos baseiam&#8208;se principalmente em relatos de casos isolados&#44; o que n&#227;o &#233; suficiente para recomendar seu uso no ambiente cl&#237;nico&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">86</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Perfil de seguran&#231;a da imunoterapia direcionada para HS</span><p id="par0230" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a dos medicamentos anti&#8208;TNF&#8208;&#945; foi discutido em se&#231;&#227;o anterior &#40;ver Psor&#237;ase&#41;&#46; Para os medicamentos anti&#8208;IL&#8208;1&#44; as considera&#231;&#245;es gerais s&#227;o semelhantes entre eles&#46; Os EA mais comuns s&#227;o rea&#231;&#245;es no local da inje&#231;&#227;o e infec&#231;&#245;es do trato respirat&#243;rio superior&#46; Outros EA relatados s&#227;o cefaleia&#44; dor abdominal&#44; diarreia e sintomas semelhantes aos da gripe&#46;<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">89</span></a></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Pioderma gangrenoso</span><p id="par0235" class="elsevierStylePara elsevierViewall">O pioderma gangrenoso &#40;PG&#41; &#233; dermatose neutrof&#237;lica caracterizada por &#250;lceras cut&#226;neas cr&#244;nicas e recorrentes com borda necrol&#237;tica&#44; com incid&#234;ncia estimada de 3&#8208;10&#47;1&#46;000&#46;000 de casos por ano&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a> Atualmente&#44; n&#227;o existem medicamentos aprovados pela FDA para essa doen&#231;a&#46; Recentemente&#44; novas terapias imunol&#243;gicas direcionadas t&#234;m sido utilizadas com algum sucesso para tratar casos refrat&#225;rios de PG&#44; mas ensaios cl&#237;nicos s&#227;o necess&#225;rios para estabelecer a real efic&#225;cia dessas terapias&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#8211;93</span></a></p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Crit&#233;rios de eligibilidade</span><p id="par0240" class="elsevierStylePara elsevierViewall">Sugere&#8208;se considerar a imunoterapia direcionada no PG ap&#243;s estudo completo para estabelecer o diagn&#243;stico dessa condi&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> A doen&#231;a deve ser recalcitrante ou de intensidade moderada a grave &#40;ASC &#62;<span class="elsevierStyleHsp" style=""></span>10&#37;&#44; locais anat&#244;micos complexos ou dor excruciante&#41;&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Terapia</span><p id="par0245" class="elsevierStylePara elsevierViewall">Existem poucas terapias direcionadas para o PG que devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46; O medicamento com mais dados para o tratamento do PG &#233; o infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> O infliximabe demonstrou melhora das les&#245;es na quarta semana &#40;20&#47;29 pacientes&#41;&#44; com remiss&#227;o completa em 21&#37; na sexta semana&#46;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a> O infliximabe tamb&#233;m tem sido utilizado com sucesso em combina&#231;&#227;o com outros medicamentos &#40;corticosteroides sist&#234;micos orais&#44; azatioprina&#44; micofenolato de mofetil e ciclosporina&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1250"><span class="elsevierStyleSup">92&#44;93&#44;95</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">H&#225; relatos de casos de PG tratados com adalimumabe e etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a> Com base nesses dados observacionais&#44; n&#227;o foram encontradas diferen&#231;as significantes nas taxas de resposta parcial ou completa ao infliximabe&#44; adalimumabe e etanercepte&#46; Em uma revis&#227;o semissistem&#225;tica sobre inibidores de TNF&#8208;&#945;&#44; foi encontrada taxa de resposta parcial de 87&#37; e resposta completa de 67&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a> O corticosteroide e a ciclosporina podem atingir 90&#37; de taxa de resposta parcial e apenas 47&#37; de taxa de resposta completa ap&#243;s seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Medicamentos anti&#8208;IL&#8208;1 tamb&#233;m t&#234;m sido utilizados para tratar PG&#46;<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">91</span></a> H&#225; 29 casos relatados na literatura do uso de anakinra em pacientes com comorbidades como artrite reumatoide&#44; psor&#237;ase e s&#237;ndromes PASH &#40;pioderma gangrenoso&#44; acne e hidradenite supurativa&#41; e PAPA &#40;artrite piog&#234;nica&#44; pioderma gangrenoso e acne&#41; na dose de 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#44;92</span></a> Em um ensaio n&#227;o controlado&#44; canaquinumabe foi usado em cinco pacientes com PG refrat&#225;rio a esteroides&#46; Quatro mostraram redu&#231;&#227;o no tamanho da les&#227;o&#8208;alvo e tr&#234;s alcan&#231;aram remiss&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">Outras terapias imunol&#243;gicas direcionadas usadas com sucesso s&#227;o ustequinumabe &#40;anti&#8208;IL&#8208;12&#47;23&#41;<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">97</span></a> e ruxolitinibe &#40;anti&#8208;JAK1&#8208;2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">91&#44;92</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Perfil de seguran&#231;a da imunoterapia direcionada para PG</span><p id="par0265" class="elsevierStylePara elsevierViewall">H&#225; casos relatados de indu&#231;&#227;o paradoxal de PG com o uso de adalimumabe&#44; etanercepte e&#44; em menor n&#250;mero&#44; com infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">As rea&#231;&#245;es adversas espec&#237;ficas do canaquinumabe s&#227;o piora da artrite reumatoide&#44; pirexia&#44; v&#244;mitos&#44; sinusite e artralgia e&#44; para anakinra&#44; ganho ponderal&#44; dor musculoesquel&#233;tica e vertigem&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Urtic&#225;ria espont&#226;nea cr&#244;nica</span><p id="par0275" class="elsevierStylePara elsevierViewall">A urtic&#225;ria espont&#226;nea cr&#244;nica &#40;UEC&#41; &#233; definida pelo aparecimento de p&#225;pulas pruriginosas transit&#243;rias e&#47;ou angioedema por pelo menos seis semanas sem um gatilho reconhec&#237;vel&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">98</span></a> A preval&#234;ncia global de UEC &#233; de 1&#44;1&#37;&#44; de acordo com a Global Burden of Disease&#46;<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">99</span></a></p><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Crit&#233;rios de eligibilidade</span><p id="par0280" class="elsevierStylePara elsevierViewall">Adultos e adolescentes com 12 anos ou mais podem ser considerados para terapia imunol&#243;gica direcionada se permanecerem sintom&#225;ticos apesar do tratamento com anti&#8208;histam&#237;nicos H1 at&#233; quatro vezes a dose padr&#227;o&#44; ou se persistirem sintom&#225;ticos com a terapia combinada &#40;anti&#8208;histam&#237;nicos H1 quatro vezes a dose padr&#227;o mais anti&#8208;histam&#237;nicos H2 e&#47;ou antagonista do receptor de leucotrieno&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1280"><span class="elsevierStyleSup">98&#44;100</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Terapia</span><p id="par0285" class="elsevierStylePara elsevierViewall">Existe apenas uma imunoterapia direcionada atualmente aprovada para UEC&#44; e outras op&#231;&#245;es devem ser selecionadas em casos refrat&#225;rios ou no contexto de pesquisa &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a>&#41;&#46; O omalizumabe&#44; um mAb anti&#8208;IgE&#44; foi aprovado pela FDA em 2014 para uso em pacientes &#62;<span class="elsevierStyleHsp" style=""></span>12 anos com UEC&#46; Essa autoriza&#231;&#227;o foi baseada em dois ECRs &#40;ASTERIA I e ASTERIA II&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">101</span></a> ECRs mostraram que&#44; em 40 semanas&#44; 75&#44;3&#37; dos pacientes com UEC obtiveram resposta completa e 14&#44;6&#37; tiveram resposta parcial&#46;<a class="elsevierStyleCrossRef" href="#bib1300"><span class="elsevierStyleSup">102</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0290" class="elsevierStylePara elsevierViewall">O ligelizumabe&#44; um mAb anti&#8208;IgE&#44; ainda est&#225; em estudo&#44; mas ensaios cl&#237;nicos recentes para o tratamento da UEC est&#227;o mostrando efic&#225;cia semelhante ao omalizumabe&#46;<a class="elsevierStyleCrossRefs" href="#bib1305"><span class="elsevierStyleSup">103&#44;104</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Lirentelimabe &#233; mAb de lectina 8 semelhante &#224; imunoglobulina com liga&#231;&#227;o ao &#225;cido antissi&#225;lico &#40;anti&#8208;SIGLEC&#8208;8&#44; um receptor inibit&#243;rio presente em eosin&#243;filos e mast&#243;citos&#41;&#46; A liga&#231;&#227;o ao SIGLEC&#8208;8 induz a morte de eosin&#243;filos&#44; inibe a degranula&#231;&#227;o mediada por IgE dos mast&#243;citos e a s&#237;ntese <span class="elsevierStyleItalic">de novo</span> de prostaglandina D2&#46; Os resultados de um estudo de fase 2 com lirentelimabe para o tratamento de UEC e para o tratamento de urtic&#225;ria induz&#237;vel demonstraram 92&#37; de resposta completa na semana 22 e apenas 36&#37; de resposta completa em pacientes anteriormente refrat&#225;rios ao tratamento com omalizumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">O dupilumabe demonstrou resposta parcial em relatos de casos&#46;<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a> Benralizumabe e mepolizumabe&#44; ambas mol&#233;culas experimentais anti&#8208;IL&#8208;5R e anti&#8208;IL&#8208;5&#44; respectivamente&#44; tamb&#233;m foram utilizados&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">107</span></a> Em ambos os casos&#44; os pacientes tratados apresentaram melhora cl&#237;nica&#46;<a class="elsevierStyleCrossRef" href="#bib1330"><span class="elsevierStyleSup">108</span></a> O secuquinumabe tem sido usado em relatos de casos para o tratamento de UEC em pacientes refrat&#225;rios ao tratamento com anti&#8208;histam&#237;nicos H1 e omalizumabe&#44; mostrando redu&#231;&#227;o significante na atividade da doen&#231;a desde o in&#237;cio&#46;<a class="elsevierStyleCrossRef" href="#bib1335"><span class="elsevierStyleSup">109</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Perfil de seguran&#231;a da imunoterapia direcionada para UEC</span><p id="par0305" class="elsevierStylePara elsevierViewall">Os efeitos adversos mais comuns&#44; mas control&#225;veis&#44; do omalizumabe s&#227;o cefaleia&#44; dor abdominal superior&#44; pirexia e rea&#231;&#227;o local no local da inje&#231;&#227;o&#46; Efeitos adversos mais graves&#44; como rea&#231;&#227;o anafil&#225;tica&#44; s&#237;ncope e angioedema&#44; foram relatados com frequ&#234;ncia inferior a 1&#47;1&#46;000&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">98</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">Para o lirentelimabe&#44; os EA mais comuns inclu&#237;ram rea&#231;&#245;es relacionadas &#224; infus&#227;o&#44; nasofaringite e cefaleia&#46; N&#227;o ocorreram EA graves relacionados ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Alopecia areata</span><p id="par0315" class="elsevierStylePara elsevierViewall">Alopecia areata &#40;AA&#41; &#233; doen&#231;a autoimune decorrente da perda do privil&#233;gio imunol&#243;gico do fol&#237;culo piloso&#46; Recentemente&#44; a FDA aprovou o baricitinibe para tratamento de AA &#40;2022&#41; e muitos outros JAKis est&#227;o em estudo avan&#231;ado para aprova&#231;&#227;o&#46;</p><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Crit&#233;rios de eligibilidade</span><p id="par0320" class="elsevierStylePara elsevierViewall">Os pacientes devem ser considerados para tratamento com JAKis se tiverem doen&#231;a moderada ou grave &#40;perda total de cabelos &#8805; 30&#37; do couro cabeludo por pelo menos tr&#234;s a seis meses&#44; medida utilizando o escore da ferramenta <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> &#91;SALT&#93; ou resposta refrat&#225;ria ao tratamento convencional nos &#250;ltimos seis meses&#41;&#46; N&#227;o h&#225; limita&#231;&#227;o quanto &#224; dura&#231;&#227;o anterior da alopecia e os estudos consideraram pacientes com ampla varia&#231;&#227;o de dura&#231;&#227;o da AA como candidatos ao tratamento com JAKis&#46;<a class="elsevierStyleCrossRefs" href="#bib1340"><span class="elsevierStyleSup">110&#44;111</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Terapia</span><p id="par0325" class="elsevierStylePara elsevierViewall">Existe apenas uma imunoterapia direcionada atualmente aprovada para AA&#44; mas outras op&#231;&#245;es t&#234;m sido utilizadas com sucesso e devem ser selecionadas de acordo com diferentes crit&#233;rios cl&#237;nicos em cada paciente &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabela 6</a>&#41;&#46; A FDA aprovou o baricitinibe &#40;2022&#41;&#44; um JAK 1&#8208;2i&#44; para o tratamento de AA em adultos&#46; Sua efic&#225;cia foi avaliada em dois ensaios randomizados&#44; duplo&#8208;cegos e controlados por placebo &#40;BRAVE AA&#8208;1 e BRAVE AA&#8208;2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a> Os pacientes nesses estudos receberam 2 ou 4<span class="elsevierStyleHsp" style=""></span>mg de baricitinibe por dia&#46; Os resultados finais na semana 36 mostraram resposta adequada de 22&#37; com 2<span class="elsevierStyleHsp" style=""></span>mg e 38&#37; com 4<span class="elsevierStyleHsp" style=""></span>mg Resultados semelhantes foram observados no BRAVE AA&#8208;2 &#40;19&#37; de resposta adequada com 2<span class="elsevierStyleHsp" style=""></span>mg e 35&#37; com 4<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a> Tofacitinibe&#44; um JAK 1&#8208;3i&#44; tem sido usado para tratar casos moderados a graves de AA com &#62;<span class="elsevierStyleHsp" style=""></span>50&#37; de perda de cabelo no couro cabeludo em adultos&#44; alcan&#231;ando resposta completa em 20&#37; dos pacientes tratados e 77&#37; de resposta parcial em quatro a 18 meses de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">112</span></a> Em 2023&#44; a FDA aprovou o ritlecitinibe para o tratamento da AA em pessoas com mais de 12 anos com base nos resultados do estudo ALLEGRO&#44; no qual 23&#37; dos pacientes alcan&#231;aram recupera&#231;&#227;o capilar de pelo menos 80&#37; ap&#243;s seis meses de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1355"><span class="elsevierStyleSup">113</span></a> Ruxolitinibe &#233; o &#250;ltimo JAKi usado para o tratamento da AA&#44; atingindo de forma geral resposta em 93&#37; dos pacientes e resposta completa em 21&#37; dos pacientes tratados em seis meses de seguimento&#46;<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">111</span></a></p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Perfil de seguran&#231;a da imunoterapia direcionada para AA</span><p id="par0330" class="elsevierStylePara elsevierViewall">O perfil de seguran&#231;a dos medicamentos inibidores de JAK foi extensivamente estudado e&#44; em geral&#44; todos os JAKis utilizados para o tratamento de AA s&#227;o bem tolerados&#46; Infec&#231;&#245;es do trato respirat&#243;rio superior&#44; hipercolesterolemia&#44; creatina fosfoquinase elevada&#44; cefaleia&#44; diarreia e nasofaringite s&#227;o os EA relatados com mais frequ&#234;ncia&#46; Os efeitos adversos menos comuns inclu&#237;ram outras infec&#231;&#245;es&#44; como herpes&#8208;z&#243;ster&#44; herpes&#8208;simples&#44; infec&#231;&#245;es do trato urin&#225;rio e gastroenterite&#46;<a class="elsevierStyleCrossRefs" href="#bib1340"><span class="elsevierStyleSup">110&#8211;112</span></a></p></span></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Doen&#231;as bolhosas autoimunes</span><p id="par0335" class="elsevierStylePara elsevierViewall">As doen&#231;as bolhosas autoimunes s&#227;o um grupo de doen&#231;as caracterizadas pela produ&#231;&#227;o de autoanticorpos contra mol&#233;culas de ades&#227;o da pele&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> Essa revis&#227;o ir&#225; discutir a imunoterapia direcionada para p&#234;nfigo vulgar &#40;PV&#41;&#44; p&#234;nfigo foli&#225;ceo &#40;PF&#41; e penfigoide bolhoso &#40;PB&#41;&#46;</p><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Crit&#233;rios de eligibilidade</span><p id="par0340" class="elsevierStylePara elsevierViewall">Os pacientes s&#227;o candidatos &#224; imunoterapia direcionada como op&#231;&#227;o de primeira linha em casos de PV&#47;PF moderado a grave de in&#237;cio recente ou em pacientes previamente tratados que n&#227;o alcan&#231;am remiss&#227;o cl&#237;nica com corticosteroides sist&#234;micos ou adjuvantes imunossupressores&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> A gravidade da doen&#231;a deve ser medida por meio do escore do <span class="elsevierStyleItalic">Pemphigus Disease and Area Index</span> &#40;PDAI&#41;&#46; O envolvimento m&#250;ltiplo das mucosas &#40;oral&#44; nasofar&#237;ngea&#44; conjuntival&#44; genital&#41; ou PDAI &#8805;<span class="elsevierStyleHsp" style=""></span>15 s&#227;o considerados doen&#231;a moderada&#46; Pacientes com escore PDAI &#8805;<span class="elsevierStyleHsp" style=""></span>45 ou les&#245;es orais&#44; disfagia e perda ponderal apresentam doen&#231;a grave&#46;<a class="elsevierStyleCrossRefs" href="#bib1365"><span class="elsevierStyleSup">115&#44;116</span></a></p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Terapia</span><p id="par0345" class="elsevierStylePara elsevierViewall">O rituximabe &#233; o &#250;nico medicamento biol&#243;gico aprovado pela FDA &#40;2018&#41; para doen&#231;as bolhosas e &#233; considerado a primeira op&#231;&#227;o terap&#234;utica para PV e PF pelas diretrizes internacionais&#46;<a class="elsevierStyleCrossRef" href="#bib1370"><span class="elsevierStyleSup">116</span></a> Essa aprova&#231;&#227;o foi baseada nos resultados do Rituxi3&#44;<a class="elsevierStyleCrossRef" href="#bib1365"><span class="elsevierStyleSup">115</span></a> no qual 89&#37; dos pacientes com p&#234;nfigo tratados com rituximabe e prednisolona oral estavam livres da doen&#231;a e sem necessidade de qualquer tratamento adicional ap&#243;s 24 meses&#44; em compara&#231;&#227;o com 34&#37; com prednisolona isoladamente&#46; O tratamento com rituximabe tamb&#233;m reduziu a dose de corticosteroides necess&#225;ria para a remiss&#227;o cl&#237;nica&#44; reduzindo os efeitos adversos associados a altas doses de esteroides<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">117</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0035">tabela 7</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0035"></elsevierMultimedia><p id="par0350" class="elsevierStylePara elsevierViewall">Efgartigimode &#233; anticorpo IgG1 humano direcionado ao receptor Fc neonatal&#46; O bloqueio do receptor Fc neonatal diminui a disponibilidade de anticorpos IgG patog&#234;nicos e foi testado para o tratamento de PF e PV&#46;<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">118</span></a> Em um ensaio de fase 2&#44; a utiliza&#231;&#227;o isolada de efgartigimode demonstrou controle precoce da doen&#231;a em 90&#37; dos pacientes ap&#243;s 17 dias&#46; Combinado com prednisona&#44; levou &#224; remiss&#227;o cl&#237;nica completa em 64&#37; dos pacientes ap&#243;s seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">119</span></a> Dois ensaios cl&#237;nicos de fase 3 avaliando a efic&#225;cia e a seguran&#231;a do efgartigimode em adultos com p&#234;nfigo &#40;<a href="ctgov:NCT04598451">NCT04598451</a> e <a href="ctgov:NCT04598477">NCT04598477</a>&#41; est&#227;o em andamento&#46;<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">117</span></a></p><p id="par0355" class="elsevierStylePara elsevierViewall">O fator de ativa&#231;&#227;o de c&#233;lulas B &#40;BAFF&#41;&#44; tamb&#233;m conhecido como estimulador de linf&#243;citos B &#40;BLyS&#41;&#44; &#233; um importante ativador de c&#233;lulas B&#46;<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">120</span></a> O ianalumabe &#233; um mAb experimental que se liga ao BLyS&#46; Um ensaio cl&#237;nico de fase 2 foi conduzido para determinar as doses&#44; o benef&#237;cio e a seguran&#231;a do ianalumabe em pacientes com PV&#44; mostrando diminui&#231;&#227;o de 73&#37; no escore m&#233;dio do PDAI na semana 12 em sete pacientes com p&#234;nfigo em compara&#231;&#227;o com controles tratados com placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a></p><p id="par0360" class="elsevierStylePara elsevierViewall">Tratamento com rituximabe&#44; omalizumabe e dupilumabe est&#225; relatado em pacientes com PB&#46; Cao et al&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> conduziram uma revis&#227;o sistem&#225;tica para avaliar o uso desses tr&#234;s produtos biol&#243;gicos em pacientes com PB refrat&#225;rios ao uso de outras terapias sist&#234;micas&#44; como corticosteroides sist&#234;micos&#44; metotrexato&#44; micofenolato de mofetil&#44; azatioprina&#44; ciclosporina e ciclofosfamida&#46; Os autores descobriram que o rituximabe levou &#224; remiss&#227;o completa em 70&#44;5&#37; e &#224; remiss&#227;o parcial em 23&#44;8&#37; dos pacientes ap&#243;s seis meses de seguimento&#44; com taxa de recorr&#234;ncia de 20&#44;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> O omalizumabe levou &#224; remiss&#227;o completa em 67&#44;9&#37; e &#224; remiss&#227;o parcial em 20&#44;8&#37; dos pacientes em seis meses&#44; com taxa de recorr&#234;ncia de 5&#44;7&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1400"><span class="elsevierStyleSup">122</span></a> O dupilumabe levou &#224; remiss&#227;o completa em 66&#44;7&#37; e &#224; remiss&#227;o parcial em 19&#44;4&#37; dos pacientes ap&#243;s 4&#44;5 meses de tratamento&#44; com taxa de recorr&#234;ncia de 5&#44;6&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib1405"><span class="elsevierStyleSup">123&#44;124</span></a></p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Perfil de seguran&#231;a da imunoterapia direcionada para doen&#231;as bolhosas</span><p id="par0365" class="elsevierStylePara elsevierViewall">Embora o rituximabe seja um excelente medicamento para PV ou PF graves&#44; ele tamb&#233;m est&#225; associado a EA graves bem conhecidos&#46; Os mais bem documentados s&#227;o rea&#231;&#245;es &#224; infus&#227;o&#44; infec&#231;&#245;es&#44; dist&#250;rbios card&#237;acos e casos de leucoencefalopatia multifocal progressiva fatal&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a> A maioria desses EA pode ser controlada clinicamente se forem reconhecidos no est&#225;gio inicial&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">Um estudo recente mostrou que o tratamento com rituximabe foi associado a menor risco de desenvolvimento de comorbidades cardiovasculares e metab&#243;licas&#44; por isso pode ser particularmente preferido em indiv&#237;duos com fatores de risco cardiovasculares e metab&#243;licos&#44; para os quais os EA relacionados aos corticosteroides devem ser rigorosamente evitados&#46;<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">125</span></a></p></span></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Outras doen&#231;as dermatol&#243;gicas</span><p id="par0375" class="elsevierStylePara elsevierViewall">Ser&#227;o consideradas nesta se&#231;&#227;o doen&#231;as com evid&#234;ncias escassas &#40;pequenos ensaios ou s&#233;ries de casos&#44; evid&#234;ncias indiretas de outras doen&#231;as ou ensaios em andamento sem resultados&#41; ou com terapia t&#243;pica&#44; mas sem terapia sist&#234;mica dispon&#237;vel &#40;<a class="elsevierStyleCrossRef" href="#tbl0040">tabela 8</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0040"></elsevierMultimedia><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">S&#237;ndrome de Stevens&#8208;Johnson&#47;necr&#243;lise epid&#233;rmica t&#243;xica</span><p id="par0380" class="elsevierStylePara elsevierViewall">A s&#237;ndrome de Stevens&#8208;Johnson&#47;necr&#243;lise epid&#233;rmica t&#243;xica &#40;SSJ&#47;NET&#41; &#233; doen&#231;a mucocut&#226;nea grave e rara causada pela exposi&#231;&#227;o a determinados medicamentos &#8211; os mais frequentes s&#227;o sulfonamidas&#44; anticonvulsivantes&#44; anti&#8208;inflamat&#243;rios n&#227;o esteroides&#44; alopurinol e penicilinas&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Em virtude de sua baixa incid&#234;ncia&#44; o uso relatado de produtos biol&#243;gicos nessa doen&#231;a foi limitado principalmente a s&#233;ries de casos e apenas dois ensaios&#46;<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">126&#8211;128</span></a> Com os dados atuais&#44; a efic&#225;cia e a seguran&#231;a da monoterapia biol&#243;gica e da terapia combinada n&#227;o podem ser determinadas de maneira conclusiva&#44; e o papel final desses medicamentos ainda est&#225; sendo pesquisado&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall">O maior n&#250;mero de casos relatados est&#225; relacionado com o etanercepte&#46; O regime terap&#234;utico mais utilizado &#233; 25<span class="elsevierStyleHsp" style=""></span>mg &#40;em crian&#231;as com peso &#60;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; e 50<span class="elsevierStyleHsp" style=""></span>mg &#40;adultos ou crian&#231;as &#62;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; nos dias 0 e 3&#46; A monoterapia com etanercepte alcan&#231;ou reepiteliza&#231;&#227;o em 13 dias e taxa de mortalidade de 7&#44;6&#37;&#44; enquanto os pacientes tratados com etanercepte em combina&#231;&#227;o com corticosteroides alcan&#231;aram reepiteliza&#231;&#227;o em 11&#44;1 dias e tiveram taxa de mortalidade de 7&#44;7&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Wang et al&#46;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a> conduziram um ECR no qual 96 pacientes com SSJ&#47;NET foram inclu&#237;dos para comparar os efeitos do etanercepte aos corticosteroides tradicionais&#46; O estudo demonstrou que o etanercepte diminuiu a mortalidade prevista com base no escore de gravidade espec&#237;fico para NET &#40;SCORTEN&#41; em cerca de 9&#44;4&#37; em compara&#231;&#227;o aos corticosteroides tradicionais&#46;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a> O infliximabe geralmente era usado na dose de 5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Em relatos de casos de pacientes tratados com infliximabe em monoterapia&#44; o n&#250;mero m&#233;dio de dias at&#233; a reepiteliza&#231;&#227;o foi de 10&#44;4 e n&#227;o houve relatos de mortalidade&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a> Nos relatos de casos de NET tratados com a combina&#231;&#227;o infliximabe&#47;corticosteroides sist&#234;micos&#44; o n&#250;mero m&#233;dio de dias para reepiteliza&#231;&#227;o foi de 14&#44;2 e a taxa m&#233;dia de mortalidade foi de 22&#44;2&#37;&#46; Uma revis&#227;o Cochrane recente mostrou que o etanercepte 25<span class="elsevierStyleHsp" style=""></span>mg &#40;50<span class="elsevierStyleHsp" style=""></span>mg se &#62;<span class="elsevierStyleHsp" style=""></span>65<span class="elsevierStyleHsp" style=""></span>kg&#41; duas vezes por semana at&#233; a cicatriza&#231;&#227;o das les&#245;es cut&#226;neas pode reduzir a mortalidade espec&#237;fica da doen&#231;a em compara&#231;&#227;o com os corticosteroides &#40;RR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;51&#59; IC95&#37; 0&#44;16&#8208;1&#44;63&#41;&#46; com poss&#237;veis benef&#237;cios e poss&#237;veis danos&#46;<a class="elsevierStyleCrossRef" href="#bib1435"><span class="elsevierStyleSup">129</span></a></p><p id="par0390" class="elsevierStylePara elsevierViewall">Em rela&#231;&#227;o ao uso de imunoterapia direcionada utilizada na SSJ&#47;NET em compara&#231;&#227;o aos corticosteroides&#44; n&#227;o houve diferen&#231;a estat&#237;stica observada entre os dois grupos de tratamento na incid&#234;ncia de EA&#59; entretanto&#44; houve menor incid&#234;ncia de hemorragia gastrintestinal relatada com produtos biol&#243;gicos <span class="elsevierStyleItalic">versus</span> corticosteroide tradicional&#46;<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">126&#44;127&#44;130</span></a></p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">DiHS&#47;DRESS</span><p id="par0395" class="elsevierStylePara elsevierViewall">A s&#237;ndrome de hipersensibilidade induzida por medicamentos&#47;rea&#231;&#227;o a medicamentos com eosinofilia e sintomas sist&#234;micos &#40;DiHS&#47;DRESS&#41; &#233; uma rea&#231;&#227;o medicamentosa grave com mortalidade de 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">131</span></a> Casos de sucesso foram publicados usando terapia imunol&#243;gica direcionada&#46; Em um relato recente estudando dois casos de DRESS associado a envolvimento mioc&#225;rdico&#44; tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia foi usado &#40;por tr&#234;s anos&#41; sequencialmente associado a corticosteroides&#44; ciclosporina&#44; metotrexato ou IVIg&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a> Os dois casos demonstraram remiss&#227;o quando o tofacitinibe foi utilizado&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a></p><p id="par0400" class="elsevierStylePara elsevierViewall">Um estudo relato de casos anterior de 10 pacientes com DRESS demonstrou tempo m&#233;dio de cicatriza&#231;&#227;o de 8&#44;5 dias ap&#243;s inje&#231;&#227;o subcut&#226;nea de 50<span class="elsevierStyleHsp" style=""></span>mg de etanercepte&#46;<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">131</span></a> Por fim&#44; h&#225; um &#250;nico relato de caso de paciente tratado com sucesso com mepolizumabe&#46;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">133</span></a></p></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">L&#237;quen plano</span><p id="par0405" class="elsevierStylePara elsevierViewall">O adalimumabe &#233; a &#250;nica imunoterapia direcionada recomendada pelas diretrizes internacionais para o tratamento de LP cut&#226;neo e mucoso&#44; em casos refrat&#225;rios graves&#46;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a> Seu uso melhora o prurido e obt&#233;m a cicatriza&#231;&#227;o das les&#245;es cut&#226;neas em um per&#237;odo de seis meses&#46;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a> Outra imunoterapia direcionada para LP &#233; o ruxolitinibe t&#243;pico&#44; que est&#225; em estudos de fase 2 para tratar LP cut&#226;neo&#46;<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">135</span></a> Ele foi testado como creme a 1&#44;5&#37; duas vezes ao dia&#44; mostrando melhora no escore cl&#237;nico e escore modificado do <span class="elsevierStyleItalic">Composite Assessment of Index Lesion Severity</span> &#40;mCAILS&#41; ap&#243;s quatro semanas de tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">135</span></a> O uso de tofacitinibe foi relatado em s&#233;ries de casos em doses de 5<span class="elsevierStyleHsp" style=""></span>mg &#40;duas vezes ao dia&#41; em per&#237;odos de seguimento variando de dois a nove meses para tratar l&#237;quen plano pilar &#40;LPP&#41; e LP hipertr&#243;fico&#44; mostrando melhora cl&#237;nica e no escore <span class="elsevierStyleItalic">LPP Activity Index</span> &#40;LPPAI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">136</span></a> O relato do uso de outros JAKis&#44; como upadacitinibe ou baricitinibe&#44; &#233; escasso&#46; H&#225; 13 pacientes relatados em s&#233;ries de casos e relatos de casos usando baricitinibe para LPP&#44; com cinco alcan&#231;ando resolu&#231;&#227;o parcial&#44; sete sem resolu&#231;&#227;o e apenas um com resolu&#231;&#227;o completa&#46; H&#225; apenas dois relatos de caso com o uso de upadacitinibe para LP&#44; e ambos obtiveram resolu&#231;&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">137</span></a> Por fim&#44; estudos de fase 2 est&#227;o sendo realizados atualmente com ixequizumabe &#40;LP cut&#226;neo&#44; LPP&#41; e secuquinumabe &#40;LP cut&#226;neo&#44; LPP e LP oral&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1480"><span class="elsevierStyleSup">138</span></a></p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">L&#250;pus eritematoso cut&#226;neo</span><p id="par0410" class="elsevierStylePara elsevierViewall">A FDA aprovou o anifrolumabe para o l&#250;pus eritematoso sist&#234;mico &#40;LES&#41; em julho de 2021&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">139</span></a> O anifrolumabe &#233; anticorpo monoclonal totalmente humanizado que inibe seletivamente o receptor 1 do IFN&#8208;&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">139</span></a> No ECR TULIP&#8208;2&#44; o anifrolumabe foi testado para o tratamento do LES&#44; em pacientes com doen&#231;a cut&#226;nea pelo menos moderadamente grave&#44; e 49&#37; dos pacientes obtiveram redu&#231;&#227;o no escore <span class="elsevierStyleItalic">Cutaneous Lupus Erythematosus Disease Area and Severity Index</span> &#40;CLASI&#41; &#8805; 50&#37; em compara&#231;&#227;o com 25&#37; no grupo placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">140</span></a> O belimumabe &#233; outro medicamento aprovado pela FDA em 2011 para tratamento do LES&#46; Ainda n&#227;o h&#225; resultados finais espec&#237;ficos para a pele em rela&#231;&#227;o a esse medicamento no LEC&#46;<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">141</span></a></p></span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Vitiligo</span><p id="par0415" class="elsevierStylePara elsevierViewall">Para o vitiligo&#44; o ruxolitinibe t&#243;pico foi aprovado pela FDA em 2022 para o tratamento de doen&#231;a n&#227;o segmentar comprometendo &#60;<span class="elsevierStyleHsp" style=""></span>10&#37; da ASC em pacientes adultos e pedi&#225;tricos com &#62;<span class="elsevierStyleHsp" style=""></span>12 anos&#46; Em dois ensaios de fase 3 &#40;TRuE&#8208;V1 e TRuE&#8208;V2&#41;&#44; os indiv&#237;duos foram randomizados para tratamento com ruxolitinibe creme a 1&#44;5&#37; ou placebo duas vezes ao dia durante duas semanas&#46; No final do per&#237;odo de tratamento de 24 semanas&#44; 30&#37; dos pacientes que receberam ruxolitinibe tiveram pelo menos 75&#37; de melhora no <span class="elsevierStyleItalic">Vitiligo Area Scoring Index</span> &#40;VASI&#41; facial&#44; em compara&#231;&#227;o com 10&#37; dos pacientes que receberam placebo&#46;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a> Tamb&#233;m nesses estudos&#44; o creme de ruxolitinibe mostrou melhora na pigmenta&#231;&#227;o acral&#44; o que historicamente tem sido uma &#225;rea refrat&#225;ria &#224; repigmenta&#231;&#227;o com fototerapia&#44; corticosteroides t&#243;picos e tacrolimus&#46;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a> Um estudo piloto com 11 pacientes com vitiligo facial usando creme de tofacitinibe 2&#37; em conjunto com UVB de banda estreita mostrou redu&#231;&#227;o de 70&#37; no escore VASI ap&#243;s dois a quatro meses&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">143</span></a> Por outro lado&#44; uma s&#233;rie de casos de 10 pacientes em uso de tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia por 10 meses e UVB de banda estreita ou fotoexposi&#231;&#227;o obteve diminui&#231;&#227;o de apenas 5&#44;4&#37; na ASC &#40;cinco pacientes&#41; e outros cinco pacientes n&#227;o alcan&#231;aram qualquer repigmenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib1510"><span class="elsevierStyleSup">144</span></a></p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Doen&#231;as granulomatosas cut&#226;neas &#40;granuloma anular e sarcoidose&#41;</span><p id="par0420" class="elsevierStylePara elsevierViewall">As doen&#231;as granulomatosas podem representar desafios terap&#234;uticos&#46; O manejo pode ser insatisfat&#243;rio com a terapia sist&#234;mica convencional&#46;<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">145</span></a> O tratamento com anti&#8208;TNF foi tentado com resultados vari&#225;veis&#46;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a> A imunoterapia direcionada para JAKis parece ser op&#231;&#227;o promissora com base nos resultados de s&#233;ries de casos recentes&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a> Tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia foi utilizado em pacientes que n&#227;o responderam aos corticosteroides&#46; Em relato de casos de apenas um paciente&#44; a remiss&#227;o completa foi obtida ap&#243;s quatro meses de tratamento&#46; Para sarcoidose &#40;tr&#234;s pacientes&#41;&#44; a mesma s&#233;rie de casos mostrou resposta completa em dois pacientes e melhora de 96&#37; em um paciente&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a> Mais ECRs s&#227;o necess&#225;rios para estabelecer o valor real dos JAKis nas doen&#231;as granulomatosas&#46;</p></span><span id="sec0215" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">S&#237;ndrome hipereosinof&#237;lica</span><p id="par0425" class="elsevierStylePara elsevierViewall">Uma s&#233;rie de casos de cinco pacientes refrat&#225;rios a esteroides tratados com tofacitinibe 5<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia mostrou remiss&#227;o completa em tr&#234;s deles e remiss&#227;o quase completa em outro&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">148</span></a> O paciente restante n&#227;o conseguiu completar o tratamento com tofacitinibe por motivos relacionados ao seguro de sa&#250;de&#44; e o tratamento foi alterado para ruxolitinibe 25<span class="elsevierStyleHsp" style=""></span>mg pela manh&#227; e 10<span class="elsevierStyleHsp" style=""></span>mg &#224; noite&#46; Esse paciente tamb&#233;m obteve remiss&#227;o completa&#46;<a class="elsevierStyleCrossRef" href="#bib1530"><span class="elsevierStyleSup">148</span></a></p></span><span id="sec0220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Morfeia</span><p id="par0430" class="elsevierStylePara elsevierViewall">H&#225; casos de sucesso com uso de imunoterapia direcionada para casos refrat&#225;rios de morfeia&#46; Em dois pacientes com morfeia profunda generalizada associada &#224; fasci&#237;te eosinof&#237;lica que n&#227;o responderam &#224; corticoterapia&#44; tofacitinibe &#40;10<span class="elsevierStyleHsp" style=""></span>mg duas vezes ao dia&#41; foi adicionado &#224; fototerapia e ao metotrexato&#44; proporcionando melhora cl&#237;nica em ambos&#46;<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">149</span></a> Foi relatado que tocilizumabe &#40;um medicamento anti&#8208;IL&#8208;6&#41; &#233; eficaz no tratamento da morfeia panescler&#243;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib1540"><span class="elsevierStyleSup">150&#44;151</span></a> Uma adolescente de 14 anos foi tratada com sucesso com infliximabe&#46;<a class="elsevierStyleCrossRef" href="#bib1540"><span class="elsevierStyleSup">150</span></a></p></span></span></span><span id="sec0225" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Conclus&#227;o</span><p id="par0435" class="elsevierStylePara elsevierViewall">Muitas terapias imunol&#243;gicas direcionadas s&#227;o atualmente empregadas no tratamento de doen&#231;as dermatol&#243;gicas inflamat&#243;rias&#46; Algumas dessas mol&#233;culas ganharam papel importante no tratamento de doen&#231;as cut&#226;neas cr&#244;nicas e incapacitantes que n&#227;o eram anteriormente controladas com tratamentos padr&#227;o&#44; como o anti&#8208;IL&#8208;4&#47;13 na DA&#44; o anti&#8208;TNF&#8208;&#945; na HS ou os inibidores de JAK na AA&#44; gerando mudan&#231;a de paradigma no arsenal terap&#234;utico da dermatologia&#46;<a class="elsevierStyleCrossRefs" href="#bib1010"><span class="elsevierStyleSup">44&#44;152&#44;153</span></a> Al&#233;m disso&#44; os avan&#231;os na compreens&#227;o da fisiopatologia dessas doen&#231;as facilitaram abordagens terap&#234;uticas direcionadas para vias inflamat&#243;rias&#44; como o bloqueio de citocinas dependentes de JAK&#8208;STAT IL&#8208;5&#44; IL&#8208;6&#44; IL&#8208;10 e IL&#8208;13 em DiHS&#47;DRESS&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">132</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">Existem alguns aspectos cr&#237;ticos no desenvolvimento de terapias direcionadas para doen&#231;as inflamat&#243;rias da pele que devem ser considerados&#46; A seguran&#231;a em longo prazo &#233; um aspecto relevante de todos os novos medicamentos&#46; Alguns EA podem permanecer latentes durante os ensaios cl&#237;nicos&#44; aparecendo apenas com o uso prolongado&#46; Outros &#8211; em muito poucos pacientes &#8211; podem surgir desde o in&#237;cio do tratamento&#44; induzindo uma rea&#231;&#227;o paradoxal com piora do quadro cl&#237;nico sob tratamento com imunoterapia direcionada &#40;p&#46; ex&#46;&#44; PG&#44; psor&#237;ase&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0960"><span class="elsevierStyleSup">34&#44;35&#44;90</span></a> A colabora&#231;&#227;o entre ag&#234;ncias reguladoras&#44; profissionais de sa&#250;de e ind&#250;stria farmac&#234;utica &#233; essencial na vigil&#226;ncia p&#243;s&#8208;comercializa&#231;&#227;o e nos estudos de seguimento de longo prazo para avaliar a seguran&#231;a e a efic&#225;cia desses novos medicamentos&#46;<a class="elsevierStyleCrossRef" href="#bib1560"><span class="elsevierStyleSup">154</span></a></p><p id="par0445" class="elsevierStylePara elsevierViewall">Para que um medicamento seja considerado vi&#225;vel&#44; ele deve garantir resultados cl&#237;nicos superiores em compara&#231;&#227;o com os tratamentos existentes&#46; Isso levou os estudos a utilizarem vari&#225;veis clinim&#233;tricas cada vez melhores &#40;p&#46; ex&#46;&#44; PASI&#8208;75 <span class="elsevierStyleItalic">vs</span>&#46; PASI&#8208;90 na psor&#237;ase&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">12</span></a> mas n&#227;o necessariamente a melhores compara&#231;&#245;es&#46; Para comparar a efic&#225;cia entre medicamentos&#44; os pesquisadores realizaram metan&#225;lises em rede&#44; o que fornece algumas informa&#231;&#245;es&#44; mas tem suas limita&#231;&#245;es&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">44</span></a> Essa dificuldade de compara&#231;&#227;o direta com os medicamentos antigos ocorre&#44; por exemplo&#44; no caso de JAKi <span class="elsevierStyleItalic">versus</span> metotrexato na DA moderada a grave&#44; JAKi <span class="elsevierStyleItalic">versus</span> NB&#8208;UVB no vitiligo e etanercepte <span class="elsevierStyleItalic">versus</span> prednisona na DRESS&#46;<a class="elsevierStyleCrossRefs" href="#bib0880"><span class="elsevierStyleSup">18&#44;44&#44;133&#44;142</span></a> Faltam estudos que avaliem o impacto econ&#244;mico dessas decis&#245;es e que possam ajudar a aumentar o acesso a essas novas terapias&#46;<a class="elsevierStyleCrossRef" href="#bib1565"><span class="elsevierStyleSup">155</span></a></p><p id="par0450" class="elsevierStylePara elsevierViewall">Apesar da efic&#225;cia demonstrada em ensaios e estudos de evid&#234;ncias cl&#237;nicas&#44; as terapias direcionadas ainda s&#227;o subutilizadas&#44; especialmente em regi&#245;es de baixa ou m&#233;dia renda&#44; em virtude da disponibilidade limitada e da cobertura de seguro inadequada&#46; No Chile&#44; por exemplo&#44; 92&#37; da popula&#231;&#227;o n&#227;o t&#234;m cobertura para terapia direcionada para doen&#231;as cut&#226;neas&#44; o que leva a despesas pessoais&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">156</span></a> Situa&#231;&#227;o semelhante &#233; observada no Peru&#44; e condi&#231;&#245;es ligeiramente melhores no Brasil&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">156</span></a> Em uma pesquisa realizada pelo International Psoriasis Council em pa&#237;ses com poucos recursos ou em desenvolvimento&#44; incluindo Argentina&#44; Brasil&#44; Chile&#44; Col&#244;mbia&#44; M&#233;xico&#44; Peru&#44; China&#44; Egito&#44; Ir&#227;&#44; &#205;ndia e &#193;frica do Sul&#44; os dermatologistas geralmente citaram o custo como a principal barreira ao acesso &#224; terapia biol&#243;gica para a psor&#237;ase&#46;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">157</span></a></p><p id="par0455" class="elsevierStylePara elsevierViewall">A maioria das Diretrizes de Pr&#225;tica Cl&#237;nica &#40;DPC&#41; para doen&#231;as inflamat&#243;rias da pele incorpora uma estratifica&#231;&#227;o l&#243;gica do manejo m&#233;dico em diferentes est&#225;gios da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0930"><span class="elsevierStyleSup">28&#44;45&#44;75&#44;100&#44;116</span></a> Essa estratifica&#231;&#227;o pode n&#227;o refletir com precis&#227;o as condi&#231;&#245;es sociossanit&#225;rias em v&#225;rias regi&#245;es do mundo&#46; A maioria &#40;72&#44;1&#37;&#41; das DPCs dermatol&#243;gicas &#233; origin&#225;ria de pa&#237;ses com alto &#237;ndice sociodemogr&#225;fico &#40;ISD&#41;&#44; enquanto apenas uma pequena propor&#231;&#227;o vem de pa&#237;ses de m&#233;dio&#8208;alto &#40;8&#44;0&#37;&#41;&#44; m&#233;dio &#40;5&#44;3&#37;&#41; e baixo ISD &#40;1&#44;8&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">158</span></a> Geograficamente&#44; a distribui&#231;&#227;o tamb&#233;m n&#227;o &#233; uniforme&#44; correspondendo a 51&#44;8&#37; na Europa&#44; 21&#44;2&#37; na Am&#233;rica do Norte&#44; 15&#44;5&#37; na &#193;sia&#44; 4&#44;9&#37; na Am&#233;rica Latina e 4&#44;4&#37; na Austral&#225;sia&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">158</span></a> Assim&#44; as DPCs adaptadas &#224;s necessidades regionais nos pa&#237;ses em desenvolvimento ainda s&#227;o escassas e necess&#225;rias para melhor manejo dos pacientes que utilizam terapia direcionada para doen&#231;as inflamat&#243;rias da pele&#46;</p><p id="par0460" class="elsevierStylePara elsevierViewall">Esses novos moduladores imunol&#243;gicos direcionados para o tratamento de doen&#231;as inflamat&#243;rias da pele est&#227;o passando pelas mesmas etapas hist&#243;ricas de desenvolvimento pelas quais muitos medicamentos importantes atualmente em uso passaram&#46; Os dados apresentados e o elevado n&#250;mero de novos manuscritos que aparecem diariamente na literatura m&#233;dica preveem um futuro promissor para a utiliza&#231;&#227;o desses medicamentos no tratamento de doen&#231;as cr&#244;nicas da pele melhorando a qualidade de vida dos pacientes&#46;</p></span><span id="sec0230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Suporte financeiro</span><p id="par0465" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0235" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Contribui&#231;&#227;o dos autores</span><p id="par0470" class="elsevierStylePara elsevierViewall">Edinson Lopez&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0475" class="elsevierStylePara elsevierViewall">Raul Cabrera&#58; Concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p><p id="par0480" class="elsevierStylePara elsevierViewall">Crist&#243;bal Lecaros&#58; Concep&#231;&#227;o e planejamento do estudo&#59; coleta&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; reda&#231;&#227;o do manuscrito ou revis&#227;o cr&#237;tica de conte&#250;do intelectual importante&#59; revis&#227;o cr&#237;tica da literatura&#59; aprova&#231;&#227;o da vers&#227;o final do manuscrito&#46;</p></span><span id="sec0240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Conflito de interesses</span><p id="par0485" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Terapias de alvo molecular&#44; como anticorpos monoclonais &#40;mAbs&#41; e inibidores de Janus Quinase &#40;JAKis&#41;&#44; surgiram como ferramentas essenciais para o tratamento de doen&#231;as dermatol&#243;gicas&#46; Essas terapias modulam o sistema imune por vias de sinaliza&#231;&#227;o espec&#237;ficas&#44; proporcionando alternativas eficazes aos agentes imunossupressores sist&#234;micos tradicionais&#46; Esta revis&#227;o tem como objetivo fornecer um resumo atualizado das terapias imunol&#243;gicas direcionadas para doen&#231;as inflamat&#243;rias da pele&#44; considerando sua fisiopatologia&#44; efic&#225;cia&#44; dosagem e perfis de seguran&#231;a&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A revis&#227;o seguiu as diretrizes <span class="elsevierStyleItalic">Preferred Reporting Items for Systematic Reviews and Meta&#8208;analyses</span> &#40;PRISMA&#41;&#46; Uma busca sistem&#225;tica foi conduzida na base de dados PubMed nos &#250;ltimos 10 anos&#44; com foco em ensaios cl&#237;nicos randomizados&#44; relatos de casos e s&#233;ries de casos relacionados a terapias imunol&#243;gicas direcionadas em dermatologia&#46; Crit&#233;rios de elegibilidade foram aplicados e os dados foram extra&#237;dos de cada estudo&#44; incluindo dados de cita&#231;&#245;es&#44; desenho do estudo e resultados&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram identificados 1&#46;360 artigos n&#227;o duplicados com a estrat&#233;gia de busca inicial&#46; A revis&#227;o do t&#237;tulo e do resumo excluiu 1&#46;150&#44; enquanto a revis&#227;o do texto completo excluiu 50 artigos adicionais&#46; A revis&#227;o incluiu 143 estudos publicados entre 2012 e 2022&#44; destacando 39 medicamentos atualmente sob investiga&#231;&#227;o ou em uso para o tratamento de doen&#231;as inflamat&#243;rias da pele&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Limita&#231;&#245;es do estudo</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A heterogeneidade das informa&#231;&#245;es resumidas limita esta revis&#227;o&#46; Algumas recomenda&#231;&#245;es originaram&#8208;se de dados de ensaios cl&#237;nicos&#44; enquanto outras se basearam em an&#225;lises retrospectivas e pequenas s&#233;ries de casos&#46; As recomenda&#231;&#245;es provavelmente ser&#227;o atualizadas &#224; medida que novos resultados surgirem&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclus&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">As terapias direcionadas revolucionaram o tratamento de doen&#231;as cr&#244;nicas da pele&#44; oferecendo novas op&#231;&#245;es para pacientes que n&#227;o respondem aos tratamentos padr&#227;o&#46; Rea&#231;&#245;es paradoxais s&#227;o raramente observadas&#46; Mais estudos s&#227;o necess&#225;rios para compreender completamente os mecanismos e a natureza dessas terapias&#46; Em geral&#44; as terapias imunol&#243;gicas direcionadas em dermatologia representam um desenvolvimento promissor&#44; melhorando significantemente a qualidade de vida dos pacientes com doen&#231;as cr&#244;nicas inflamat&#243;rias da pele&#46;</p></span>"
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          2 => array:2 [
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          3 => array:2 [
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          4 => array:2 [
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      1 => array:2 [
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Trabalho realizado no Departamento de Dermatologia&#44; Faculdade de Medicina&#44; Universidad del Desarrollo&#8208;Cl&#237;nica Alemana de Santiago&#44; Santiago&#44; Chile&#46;</p>"
      ]
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          0 => array:4 [
            "apendice" => "<p id="par0510" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Material suplementar"
            "identificador" => "sec0250"
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        ]
      ]
    ]
    "multimedia" => array:11 [
      0 => array:7 [
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        "etiqueta" => "Figura 1"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas aprovadas pela FDA para doen&#231;as inflamat&#243;rias da pele&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Fluxograma PRISMA&#46;</p>"
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      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabela 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; IV&#44; intravenosa&#59; a&#44; anos&#59; PASI&#44; <span class="elsevierStyleItalic">Psoriasis Area and Severity Index</span>&#59; ASC&#44; &#225;rea da superf&#237;cie corporal&#59; DLQI&#44; <span class="elsevierStyleItalic">Dermatology Life Quality Index</span>&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Risanquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 150 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 150 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guselcumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 100 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 100 mg a cada 8 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tildraquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 100 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 100 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brodalumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 210 mg semanas 0&#44; 1 e 2&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; BSA ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 210 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ixequizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 160 mg semana 0 SC&#44; 80 mg semanas 2&#44; 4&#44; 6&#44; 8&#44; 10&#44; 12&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; BSA ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 80 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secuquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 300 mg semanas 0&#44;1&#44;2&#44;3 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg todos os meses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL&#8208;12&#47;23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustequinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;12&#47;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 45 mg semanas 0 e 4&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 90 mg semanas 0 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adultos&#58; 42&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 45 mg a cada 12 semanas&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>100 kg&#58; 90 mg a cada 12 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#44; 40 mg semana 1&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Certolizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 400 mg semanas 0&#44; 2 e 4&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; &#60;<span class="elsevierStyleHsp" style=""></span>90 kg&#58; 200 mg a cada duas semanas&#47;SC&#59; &#62;<span class="elsevierStyleHsp" style=""></span>90 kg&#58; 400 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Golimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 200 mg na semana 0&#44; 100 mg na semana 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#37; PASI&#8208;75 semana 14<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">25</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 50 mg mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 50 mg duas vezes por semana&#47;SC durante 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adultos&#58; 23&#37; PASI&#8208;90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;26</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 50 mg uma vez por semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK&#8208;2i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deucravacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidor de JAK&#8208;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psor&#237;ase em placas moderada a grave &#40;&#62; 10&#37; PASI&#44; ASC ou DLQI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#37; PASI&#8208;75 semana 16<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">25&#44;30&#8211;32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para psor&#237;ase</p>"
        ]
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      3 => array:8 [
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        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at2"
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            "rol" => "short"
          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; IV&#44; intravenosa&#59; EASI&#44; Eczema Area and Severity Index&#59; ASC&#44; &#225;rea de superf&#237;cie corporal&#59; IGA&#44; avalia&#231;&#227;o global do investigador&#59; SCORAD&#44; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis</span>&#44; PP&#8208;NRS&#44; <span class="elsevierStyleItalic">Peak Pruritus Numerical Rating Scale</span>&#59; DA&#44; dermatite at&#243;pica&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upadacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#8208;30 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; EASI&#8208;75 semana 16 &#40;30 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">43</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abrocitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;200 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#37; EASI&#8208;75 semana 16 &#40;200 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">50</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&#37; EASI&#8208;75 semana 16<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">51</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lebriquizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 500 mg semanas 0 e 2&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;8&#37; EASI&#8208;75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1065"><span class="elsevierStyleSup">55</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 250 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baricitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 mg uma vez ao dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#37; EASI&#8208;75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">60</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Traloquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37; EASI&#8208;75 semana 16<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">48</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoquimabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300 mg na semana 0&#44; 150 mg nas semanas 4&#44; 8 e 12&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#37; EASI&#8208;75 na semana 4<a class="elsevierStyleCrossRef" href="#bib1115"><span class="elsevierStyleSup">65</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fezaquinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;22</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg dose &#250;nica&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SCORAD decl&#237;nio de 14 pontos na semana 12<a class="elsevierStyleCrossRef" href="#bib1105"><span class="elsevierStyleSup">63</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas durante 10 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nemolizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DA grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 69&#37; no EASI na semana 12 &#40;30 mg&#41;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">64</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tezepelumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TSLP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">280 mg a cada duas semanas por tr&#234;s meses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AD grave &#40;ASC &#8805; 10&#37;&#44; IGA &#8805; 3&#44; EASI &#8805; 16&#44; SCORAD &#8805; 50&#44; PP&#8208;NRS &#8805; 4&#41; refrat&#225;ria a outros tratamentos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65&#37; EASI&#8208;50 semana 12<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">62</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#37; uso t&#243;pico&#44; uma vez&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IGA 2&#8208;3&#44; ASC 2&#8208;20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 82&#37; no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">67</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IGA 2&#8208;3&#44; ASC 2&#37;&#8208;20&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 71&#37; no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1120"><span class="elsevierStyleSup">66</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; HiSCR&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Clinical Response</span>&#59; HSSI&#44; <span class="elsevierStyleItalic">Hidradenitis Suppurativa Severity Index</span>&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 160 mg dia 0&#44; 80 mg dia 15&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#37;&#8208;59&#37; melhora na HiSCR em 50&#37; dos pacientes na semana 12<a class="elsevierStyleCrossRef" href="#bib1205"><span class="elsevierStyleSup">83</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg por semana&#47;SC ou 80 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 mg uma vez ao dia&#47;SC por 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#37; dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">86</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bermequimabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400 mg cada semana&#47;SC por 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#37; dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">87</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximab</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HS recalcitrante moderada a grave &#40;est&#225;gio de Hurley II&#8208;III&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#37;&#8208;50&#37; de melhora no HSSI na semana 8<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">84</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para hidradenite supurativa</p>"
        ]
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      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Tabela 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Tabela "
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          ]
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 5 mg&#47;kg semanas 0&#44; 2 e 6&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa&#44; 19&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1245"><span class="elsevierStyleSup">91</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 5 mg&#47;kg a cada oito semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#8208;50 mg cada semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa&#44; 30&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">77&#37; de resposta completa&#44; 14&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">94</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada semana&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anakinra&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 mg uma vez&#47;dia&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#37; de resposta completa&#44; 21&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Canaquinumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;1&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&#8208;300 mg a cada 4&#8208;8 semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#37; de resposta completa&#44; 9&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">95</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustequinumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;12&#47;23</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 90 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#37; de resposta completa&#44; 8&#37; de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">96</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 45 mg semanas 4 e 8&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doen&#231;a recalcitrante e est&#225;gio tardio com doen&#231;a moderada a grave &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#47;2 resposta completa ap&#243;s um a 15 meses<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">90</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3563625.png"
              ]
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        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para pioderma gangrenoso</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Tabela 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; UAS7&#44; <span class="elsevierStyleItalic">Urticaria Activity Score</span> por 7 dias seguidos&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omalizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&#8208;300 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75&#44;3&#37; de resposta completa em 40 semanas<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">100</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Se refrat&#225;ria&#44; considerar 600 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ligelizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&#8208;240 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#37; de resposta completa na semana 12<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">102&#44;103</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secuquinumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 150 mg nas semanas 0&#44; 1&#44; 2 e 3&#47;SC Manuten&#231;&#227;o&#58; 150 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria ao omalizumabe &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Redu&#231;&#227;o de 82&#37; no UAS7 na semana 12<a class="elsevierStyleCrossRef" href="#bib1330"><span class="elsevierStyleSup">108</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 600 mg semana 0&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria ao omalizumabe &#40;no contexto da pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em uma s&#233;rie de casos de seis pacientes<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">105</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lirentelimabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;SIGLEC&#8208;8</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose inicial&#58; 0&#44;3 mg&#47;kg no dia 0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pacientes que permanecem sintom&#225;ticos apesar da dose de anti&#8208;H1 4<span class="elsevierStyleHsp" style=""></span>&#215; &#40;no contexto de pesquisa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#37; de resposta completa em 22 semanas<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">104</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Doses subsequentes&#58; 1 mg&#47;kg nos dias 29&#44; 57&#44; 85&#44; 113 e 141&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Benralizumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;5</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 30 mg a cada quatro semanas por tr&#234;s doses&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento em UEC refrat&#225;ria ao antiH1</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56&#37; de resposta completa em 20 semanas<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 30 mg a cada oito semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;300 mg a cada quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento em UEC refrat&#225;ria ao antiH1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudos de fase 2 em andamento<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">106</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "pt" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para urtic&#225;ria espont&#226;nea cr&#244;nica</p>"
        ]
      ]
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baricitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 mg uma vez&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">35&#37;&#8208;38&#37; de restaura&#231;&#227;o capilar adequada na semana 36<a class="elsevierStyleCrossRef" href="#bib1335"><span class="elsevierStyleSup">109</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#37; de resposta completa e 58&#37; de restaura&#231;&#227;o capilar adequada durante quatro a 18 meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1345"><span class="elsevierStyleSup">111</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ritlecitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 mg uma vez&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#37; dos pacientes apresentam &#62;<span class="elsevierStyleHsp" style=""></span>80&#37; de restaura&#231;&#227;o capilar em seis meses<a class="elsevierStyleCrossRef" href="#bib1350"><span class="elsevierStyleSup">112</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AA moderada a grave 30&#37; de perda de cabelos no couro cabeludo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#37; de resposta completa e 64&#37; de restaura&#231;&#227;o capilar adequada durante seis meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1340"><span class="elsevierStyleSup">110</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; IV&#44; intravenosa&#59; PDAI&#44; <span class="elsevierStyleItalic">Pemphigus Disease and Area Index</span>&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 g em duas ocasi&#245;es com intervalo de duas semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinado com prednisona&#44; 89&#37; de resposta completa em 24 meses<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">114</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Efgartigimode&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Receptor antirreceptor Fc neonatal &#40;FcRn&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#8208;25 mg semanalmente durante quatro semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Combinado com prednisona&#44; resposta completa em 64&#37; dos pacientes em 2&#8208;41 semanas<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">118</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ianalumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;BLyS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 mg&#47;kg IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PV e PF refrat&#225;rios a esteroides &#40;no contexto de pesquisa&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 73&#37; no escore m&#233;dio de PDAI na semana 12<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">120</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rituximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;CD20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">375 mg&#47;m<span class="elsevierStyleSup">2</span> a cada 1&#8208;4 semanas at&#233; 500 mg semanalmente por duas semanas&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;5&#37; de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Omalizumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&#8208;525 mg a cada uma a quatro semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#37; de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IL&#8208;4&#47;13</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; dose &#250;nica de 600 mg&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PB refrat&#225;rio a esteroides</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;7&#37; de resposta completa em 4&#44;5 meses<a class="elsevierStyleCrossRef" href="#bib1395"><span class="elsevierStyleSup">121</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 300 mg a cada duas semanas&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para doen&#231;as bolhosas</p>"
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      9 => array:8 [
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">SC&#44; subcut&#226;nea&#59; VO&#44; via oral&#59; RC&#44; resposta completa&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Medicamento&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose e via de administra&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&#237;vel de evid&#234;ncia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grau de recomenda&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SSJ&#47;NET</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>65 kg&#58; 25 mg dias 0 e 3&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Em uso no contexto de pesquisa</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortalidade de 7&#44;6&#37;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">126</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>65 kg&#58; 50 mg dias 0 e 3&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infliximabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg&#47;kg dose &#250;nica&#47;IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Em uso no contexto de pesquisa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mortalidade de 22&#37;<a class="elsevierStyleCrossRef" href="#bib1425"><span class="elsevierStyleSup">127</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Adalimumabe</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de indu&#231;&#227;o&#58; 80 mg semana 0&#47;SC&#44; 40 mg semana 1&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#170; linha em LP mucoso&#44; 3&#170; linha em LP cut&#226;neo</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora no prurido e na cicatriza&#231;&#227;o de les&#245;es cut&#226;neas durante um per&#237;odo de seis meses<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">133</span></a></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dose de manuten&#231;&#227;o&#58; 40 mg a cada duas semanas SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes ao dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano cut&#226;neo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 7&#44;6 pontos de mCAILS em quatro semanas<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">134</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#237;quen plano pilar e l&#237;quen plano hipertr&#243;fico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 46&#37; no LPPAI em 12 semanas no l&#237;quen plano pilar<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">145</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">L&#250;pus Eritematoso Cut&#226;neo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anifrolumabe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;IFN&#8208;&#947;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">300 mg&#47;IV a cada quatro semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sintomas cut&#226;neos no contexto de l&#250;pus eritematoso sist&#234;mico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#37; dos pacientes alcan&#231;aram redu&#231;&#227;o no escore CLASI &#8805; 50&#37;<a class="elsevierStyleCrossRef" href="#bib1490"><span class="elsevierStyleSup">140</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vitiligo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37; t&#243;pico duas vezes ao dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 75&#37; no VASI em 30&#37; dos pacientes na semana 24<a class="elsevierStyleCrossRef" href="#bib1495"><span class="elsevierStyleSup">141</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inibidor de JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#37; t&#243;pico duas vezes&#47;dia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora de 70&#37; no VASI em quatro meses &#40;&#225;reas expostas ao sol&#41;<a class="elsevierStyleCrossRef" href="#bib1500"><span class="elsevierStyleSup">142</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#37; ASC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diminui&#231;&#227;o de 5&#44;4&#37; na ASC em 50&#37; dos pacientes<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">143</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Granuloma anular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;rio &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sarcoidose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em s&#233;ries de casos<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">146</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DiHS&#47;DRESS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRefs" href="#bib1445"><span class="elsevierStyleSup">131&#44;132</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etanercepte&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti&#8208;TNF&#8208;&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50 mg dose &#250;nica &#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primeira linha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRefs" href="#bib1445"><span class="elsevierStyleSup">131&#44;132</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">S&#237;ndrome hipereosinof&#237;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">147</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 mg de manh&#227;&#8208;10 mg &#224; noite&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RC &#40;apenas relatos de casos&#41;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">137</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morfeia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tofacitinibe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK 1&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 mg duas vezes&#47;dia&#47;VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Refrat&#225;ria &#224; esteroides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Melhora em relato de caso<a class="elsevierStyleCrossRef" href="#bib1535"><span class="elsevierStyleSup">149</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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Article information
ISSN: 26662752
Original language: Portuguese
DOI:10.1016/j.abdp.2024.03.009
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