Terapia direcionada para doenças imunomediadas da pele. O que o dermatologista deve saber? | Anais Brasileiros de Dermatologia (Portuguese)

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O que o dermatologista deve saber?" 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Anteriormente chamados de produtos biológicos, uma vez que eram sintetizados como produtos de organismos vivos, atualmente essas terapias também são compostas de pequenas moléculas – portanto, os termos terapia direcionada ou terapia‐alvo devem ser preferidos.<a class="elsevierStyleCrossRef" href="#bib0800">2</a> Além disso, o termo moduladores imunológicos direcionados é utilizado em livros de referência.<a class="elsevierStyleCrossRef" href="#bib0805">3</a>O mecanismo de ação é heterogêneo entre as diferentes moléculas, mas todas elas modulam o sistema imunológico por meio de impulsos estimulatórios ou inibitórios, atuando em pontos específicos das vias de sinalização da inflamação.<a class="elsevierStyleCrossRef" href="#bib0810">4</a> Sua eficácia e perfil de segurança são frequentemente homólogos aos agentes imunossupressores sistêmicos padrão ou até melhores. Como todos os novos medicamentos, eles não estão isentos de eventos adversos (EA) e seu custo representa barreira importante para sua acessibilidade.<a class="elsevierStyleCrossRef" href="#bib0815">5</a>Os primeiros exemplos de terapias imunológicas direcionadas para doenças inflamatórias em dermatologia foram os ensaios clínicos de alefacepte,<a class="elsevierStyleCrossRef" href="#bib0820">6</a> efalizumabe,<a class="elsevierStyleCrossRef" href="#bib0825">7</a> etanercepte<a class="elsevierStyleCrossRef" href="#bib0830">8</a> e infliximabe<a class="elsevierStyleCrossRef" href="#bib0835">9</a> para psoríase no início dos anos 2000. Alefacepte e efalizumabe foram substituídos por moléculas mais novas com renovação constante dos medicamentos utilizados em terapias imunológicas direcionadas para diferentes doenças inflamatórias da pele (<a class="elsevierStyleCrossRef" href="#fig0005">fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Esta revisão narrativa tem como objetivo atualizar, resumir e priorizar a grande quantidade de informações sobre importantes doenças inflamatórias cutâneas em formato prático para uso na clínica. Indicações de uso são sugeridas considerando dados atuais sobre eficácia, dose e perfil de segurança da imunoterapia direcionada.Material e métodosEsta revisão foi realizada com base nas diretrizes Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA).<a class="elsevierStyleCrossRef" href="#bib0840">10</a> Foi feita pesquisa sistemática no banco de dados Pubmed nos últimos 10 anos (janeiro de 2012 a julho de 2023; estratégia de busca, ver Material Suplementar 1). As referências de todos os estudos incluídos também foram avaliadas para identificar quaisquer estudos elegíveis adicionais. Foram selecionadas revisões sistemáticas e ensaios clínicos randomizados (RCE, em inglês). Também foram incluídos relatos de casos e séries de casos, se realizados em humanos. Os estudos foram excluídos se o produto biológico utilizado estivesse no contexto da medicina alternativa ou se a qualidade do relato fosse considerada insuficiente.Extração de dadosOs títulos e resumos de todos os artigos foram selecionados de maneira independente para elegibilidade por dois autores (E.L. e C.L.). Os textos completos dos artigos considerados potencialmente elegíveis foram avaliados criticamente e avaliados quanto à elegibilidade. Qualquer desacordo sobre a inclusão ou exclusão de um artigo entre os dois investigadores foi analisado por um terceiro investigador (RC) para chegar a um consenso. Os dados extraídos de cada estudo incluíram dados de citação (título do estudo, autores, ano de publicação), desenho do estudo (objetivo do estudo, período, cenário) e resultados (demografia da população, medidas de desfecho).ResultadosBusca na literaturaForam identificados 1.360 artigos não duplicados com a estratégia de busca inicial. A revisão do título e do resumo excluiu 1.150, enquanto a revisão do texto completo excluiu 50 artigos adicionais. Foram incluídos 143 estudos nesta revisão, como descrito no fluxograma PRISMA (<a class="elsevierStyleCrossRef" href="#fig0010">fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>PsoríaseA psoríase é doença cutânea crônica imunomediada que afeta aproximadamente 1% da população mundial.<a class="elsevierStyleCrossRefs" href="#bib0845">11–13</a> Apesar de evidências convincentes que apoiam o uso de terapias imunológicas direcionadas, a seleção de medicamento específico pode ser desafiadora.<a class="elsevierStyleCrossRef" href="#bib0860">14</a> A decisão final do tratamento deve incluir a preferência do paciente e, eventualmente, a consulta com médicos de outras especialidades para equilibrar riscos e benefícios.Critérios de eligibilidadeOs pacientes devem ser considerados para terapia imunológica direcionada em diversas circunstâncias: se houver psoríase grave,<a class="elsevierStyleCrossRefs" href="#bib0865">15–17</a> definida como envolvimento superior a 10% da área de superfície corporal (ASC) total, escore PASI (Psoriasis Area and Severity Index) ou DLQI (Dermatology Life Quality Index) >10 ou comprometimento de locais específicos (mãos, pés, couro cabeludo, rosto ou área genital); quando a psoríase causa prurido não tratável ou tem consequências emocionais graves com duração da doença superior a seis meses,<a class="elsevierStyleCrossRef" href="#bib0865">15</a> ou não responde à terapia convencional, ou não pode receber terapia sistêmica padrão em virtude do estado geral do paciente e de comorbidades ou quando o paciente tem doença grave, como psoríase eritrodérmica, pustulosa ou artrite psoriásica.<a class="elsevierStyleCrossRefs" href="#bib0865">15–17</a>TerapiaExistem múltiplas imunoterapias direcionadas para a psoríase. Terapias direcionadas como anti‐TNF‐α, anti‐IL‐17, anti‐IL‐23 e anti‐IL‐12/23 podem atingir PASI‐90 em mais pacientes do que o tratamento sistêmico anterior (p. ex., ciclosporina e metotrexato).<a class="elsevierStyleCrossRef" href="#bib0880">18</a> Os tratamentos anti‐IL‐17 (ou seja, ixequizumabe, secuquinumabe e brodalumabe) e anti‐IL‐23 (risanquizumabe, tildrakizumabe e guselcumabe) mostraram proporção maior de pacientes que alcançaram PASI‐90 em comparação com todas as intervenções sistêmicas avaliadas na última metanálise de rede.<a class="elsevierStyleCrossRef" href="#bib0880">18</a>Os inibidores de TNF‐α foram os primeiros medicamentos biológicos aprovados para o tratamento da psoríase.<a class="elsevierStyleCrossRefs" href="#bib0850">12,19</a> A metanálise mostra que, nessa classe, o infliximabe tem a maior eficácia, seguido pelo certolizumabe, adalimumabe e etanercepte.<a class="elsevierStyleCrossRefs" href="#bib0880">18,19</a> A FDA aprovou sequencialmente o etanercepte (2004), infliximabe (2005), adalimumabe (2008), golimumabe (2017) e certolizumabe (2018).Os inibidores da IL‐17 atingem eliminação total da doença (isto é, PASI‐100) em cerca de metade dos pacientes<a class="elsevierStyleCrossRefs" href="#bib0845">11,12</a> e têm início de ação mais rápido. Os medicamentos aprovados pela FDA para tratar a psoríase são secuquinumabe (2015), ixekizumabe (2016) e brodalumabe (2017).Os inibidores de IL‐23, risanquizumabe e guselcumabe, demonstraram recentemente melhor perfil de eficácia e segurança em comparação com o anti‐IL‐17 e regime de dosagem conveniente.<a class="elsevierStyleCrossRefs" href="#bib0890">20,21</a> Os medicamentos aprovados pela FDA são guselcumabe (2017), tildraquizumabe (2018) e risanquizumabe (2019). Ustequinumabe (2013) é um mAb que inibe IL‐12 e IL‐23.JAKis (deucravacitinibe, peficitinibe, baricitinibe, solcitinibe, itacitinibe, abrocitinibe, brepocitinibe, ruxolitinibe e tofacitinibe) também têm sido utilizados para o tratamento de pacientes psoriásicos.<a class="elsevierStyleCrossRefs" href="#bib0900">22,23</a> Embora ainda não haja dados completos sobre o impacto clínico final no tratamento da psoríase, ensaios recentes mostram resposta melhor do que certas terapias convencionais (p. ex., metotrexato, ciclosporina), mas inferior à terapia imunológica direcionada (p. ex., risanquizumabe).<a class="elsevierStyleCrossRef" href="#bib0880">18</a> O deucravacitinibe<a class="elsevierStyleCrossRefs" href="#bib0910">24,25</a>, um inibidor alostérico seletivo da tirosina quinase 2 (TYK2), é o único JAKi aprovado pela FDA (2022), alcançando PASI‐75 de 70% na semana 24.Nos últimos anos (2004‐2020) foram publicadas 51 diretrizes clínicas abordando o tratamento da psoríase, e 41 delas mencionam o uso de produtos biológicos.<a class="elsevierStyleCrossRef" href="#bib0920">26</a> Durante o período de 2021‐2022, várias sociedades dermatológicas atualizaram suas diretrizes clínicas considerando a aprovação de novas moléculas pelas agências reguladoras de medicamentos.<a class="elsevierStyleCrossRefs" href="#bib0925">27–33</a> As diretrizes reconhecem medicamentos anti‐IL‐23 e anti‐IL‐17 como parte dos tratamentos de primeira linha para o manejo da psoríase. Há grande preocupação em relação a seu alto custo e acessibilidade. A decisão final para a seleção de um medicamento para o tratamento do paciente psoriásico depende de diversos fatores clínicos e epidemiológicos (<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Perfil de segurança da imunoterapia direcionada para psoríaseO perfil de segurança da imunoterapia direcionada para psoríase está bem descrito; os EA mais comuns são as infecções do trato respiratório superior e reações no local da injeção para todas as classes de medicamentos.<a class="elsevierStyleCrossRefs" href="#bib0960">34,35</a> Considerações gerais devem ser tomadas em relação à reativação de tuberculose e hepatites B e C. O uso de JAKis também deve considerar infecções anteriores por membros da família Herpesvírus.<a class="elsevierStyleCrossRefs" href="#bib0970">36,37</a>As evidências atuais mostram que a imunoterapia direcionada não aumenta o risco de EA cardiovasculares importantes, como infarto do miocárdio, acidente vascular encefálico ou morte cardiovascular ou a incidência de neoplasias malignas.<a class="elsevierStyleCrossRefs" href="#bib0965">35,37–39</a>Reação adversa cutânea comum é a mudança fenotípica de psoríase para eczema atópico, que ocorre em até 1%‐12,1% dos pacientes que tomam medicamentos anti‐TNF‐α ou anti‐IL‐17/IL‐23.<a class="elsevierStyleCrossRef" href="#bib0990">40</a> O tratamento tópico foi bem‐sucedido em alguns casos, mas em outros o tratamento biológico precisa ser interrompido.Reação paradoxal – piora da psoríase e/ou novas lesões psoriásicas – foi relatada com o uso de certos medicamentos (p. ex., medicamentos anti‐TNF‐α e ustequinumabe). Essas reações geralmente não exigem a interrupção da terapia e são autolimitadas.<a class="elsevierStyleCrossRef" href="#bib0975">37</a> Outras reações adversas relevantes com a classe anti‐TNF‐α são infecção do trato urinário, dor nas costas, artralgia, prurido e erisipela, e infecções fúngicas invasivas, linfoma, insuficiência cardíaca, citopenia, indução ou exacerbação de doença desmielinizante e síndrome semelhante a lúpus (p. ex., infliximabe).<a class="elsevierStyleCrossRef" href="#bib0990">40</a>Os medicamentos anti‐IL‐17 e anti‐IL‐12/23 têm menos dados sobre seu perfil de segurança. Uma reação adversa de interesse nos inibidores de IL‐17 e IL‐12/23 é a candidíase mucocutânea (1,7% em pacientes tratados com secuquinumabe, 3,3% com ixequizumabe, 4,0% com brodalumabe e 2,3% de ustequinumabe).<a class="elsevierStyleCrossRef" href="#bib0995">41</a> Episódios de exacerbação de doença inflamatória intestinal também foram observados com o uso desses medicamentos. Pacientes com história de doença de Crohn ou colite ulcerativa devem ser tratados com outra imunoterapia direcionada.<a class="elsevierStyleCrossRef" href="#bib0975">37</a>Para os JAKis, os EA mais comuns foram reativação de herpes simples, úlceras bucais, pneumonia, COVID‐19, neoplasias malignas, incluindo linfoma, rabdomiólise, aumento da creatina fosfoquinase, aumento dos triglicerídeos e aumento das transaminases.<a class="elsevierStyleCrossRef" href="#bib0905">23</a>Com os dados disponíveis, as taxas de qualquer EA foram as mais baixas para tildraquizumabe, certolizumabe e etanercepte.<a class="elsevierStyleCrossRef" href="#bib0960">34</a> Para EA graves, os mais baixos foram para certolizumabe, risanquizumabe e etanercepte. No tratamento de longo prazo, o risanquizumabe apresentou o perfil de risco‐benefício mais favorável.<a class="elsevierStyleCrossRef" href="#bib0960">34</a>Populações especiaisGrávidas: o único mAb aprovado pela FDA para uso em pacientes grávidas é o certolizumabe pegol. É um fragmento peguilado da porção Fab dirigido contra o TNF‐α que não atravessa a membrana placentária.<a class="elsevierStyleCrossRefs" href="#bib0850">12,19</a>Pediátrica: Os mAbs autorizados pela FDA para crianças >4 anos são etanercepte e adalimumabe, secuquinumabe a partir dos 6 anos e ustequinumabe a partir dos 12 anos.<a class="elsevierStyleCrossRefs" href="#bib0880">18,19,42</a>Dermatite atópicaA dermatite atópica (DA) é doença inflamatória cutânea crônica e recidivante que afeta 2%‐5% dos adultos e 20% das crianças.<a class="elsevierStyleCrossRef" href="#bib1005">43</a> A eficácia da terapia imunológica direcionada na DA foi comprovada por vários estudos. Uma revisão sistemática recente de 60 ensaios clínicos realizados em 16.579 pacientes confirma a eficácia clínica dessas terapias direcionadas na DA.<a class="elsevierStyleCrossRef" href="#bib1010">44</a>Critérios de elegibilidadeTanto crianças quanto adultos podem ser considerados para receber terapia imunológica direcionada se tiverem doença grave, definida como envolvimento de mais de 10% da ASC total, Avaliação Global do Investigador (IGA) de pelo menos 3, escore EASI (Eczema Area and Severity Index) ≥ 16, escore SCORAD (Scoring Atopic Dermatitis) ≥ 50 e escore de gravidade da Pruritus Numerical Rating Scale (PP‐NRS) ≥ 4, ou quando o prurido é intratável ou tem consequências emocionais graves.<a class="elsevierStyleCrossRefs" href="#bib1015">45,46</a>TerapiaEstão disponíveis múltiplas terapias direcionadas para a DA que devem ser selecionadas de acordo com diferentes critérios clínicos em cada paciente (<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>). O dupilumabe demonstrou eficácia semelhante à ciclosporina em doses mais altas em pacientes com mais de 6 meses de idade, com resposta mais confiável e superioridade ao metotrexato e à azatioprina, e consideravelmente menos efeitos adversos.<a class="elsevierStyleCrossRef" href="#bib1010">44</a> Isso tornou a terapia imunológica direcionada muito promissora na DA, mas a comparação da eficácia e segurança entre as terapias direcionadas é difícil.<a class="elsevierStyleCrossRefs" href="#bib1010">44,47</a> Quatro medicamentos sistêmicos foram aprovados pela FDA (dupilumabe,<a class="elsevierStyleCrossRef" href="#bib1030">48</a> traloquinumabe,<a class="elsevierStyleCrossRef" href="#bib1035">49</a> abrocitinibe<a class="elsevierStyleCrossRef" href="#bib1040">50</a> e upadacitinibe<a class="elsevierStyleCrossRef" href="#bib1045">51</a>) e outros medicamentos estão sendo usados off‐label ou em ensaios clínicos.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Em comparação com dupilumabe, o abrocitinibe, 200mg/dia, e upadacitinibe, 30mg/dia, foram associados a reduções mais altas nos escores EASI, enquanto com baricitinibe e traloquinumabe, as reduções nos escores EASI foram semelhantes ou ligeiramente piores do que com dupilumabe.<a class="elsevierStyleCrossRef" href="#bib1010">44</a>Dupilumabe é mAb anti‐IL‐4/13 aprovado pela FDA em 2017 para o tratamento de DA moderada a grave, a partir dos 6 meses de idade.<a class="elsevierStyleCrossRef" href="#bib1050">52</a> O efeito terapêutico do dupilumabe é mediado principalmente pela inibição da subunidade alfa do receptor da IL‐4 (IL‐4Rα).<a class="elsevierStyleCrossRefs" href="#bib1055">53,54</a>Traloquinumabe é mAb anti‐IL‐13 aprovado pela FDA em 2021 para o tratamento de DA moderada a grave em adultos. Em dois ECRs, 300mg de traloquinumabe a cada duas semanas alcançou escore EASI‐75 em 25%‐33,2% dos pacientes em 16 semanas de tratamento. Esses ECRs também mostraram melhoras precoces no prurido, interferência no sono e escore DLQI. Os pacientes mantiveram essas respostas após 52 semanas de tratamento com traloquinumabe sem qualquer medicação de resgate.<a class="elsevierStyleCrossRefs" href="#bib1035">49,55</a> Lebriquizumabe, mAb que tem como alvo a IL‐13 foi avaliado em dois ensaios de fase 3 randomizados, duplo‐cegos, controlados por placebo, em pacientes maiores de 12 anos com DA moderada a grave mostrando escore EASI‐75 em 58,8% e 52,1% dos pacientes, respectivamente, na semana 16.<a class="elsevierStyleCrossRef" href="#bib1070">56</a>O abrocitinibe é inibidor de JAK‐1 aprovado pela FDA em 2022 para o tratamento de DA em adultos. Na DA moderada a grave, o abrocitinibe mostrou respostas consistentes no tratamento e não apresentou novas preocupações de segurança em comparação com o dupilumabe.<a class="elsevierStyleCrossRefs" href="#bib1020">46,57–59</a> Ele é utilizado na dose de 200mg/dia, atingindo 70% do escore EASI‐75 na semana 12 de tratamento.<a class="elsevierStyleCrossRef" href="#bib1080">58</a>Upadacitinibe é um inibidor de JAK‐1 aprovado pela FDA (2022) para o tratamento de DA em pacientes >12 anos. Ele mostra uma melhora no escore EASI‐75 de 71% na semana 16 com uma dose de 30mg/dia por via oral.<a class="elsevierStyleCrossRef" href="#bib1090">60</a>Recentemente, o baricitinibe, um inibidor de primeira geração de JAK 1‐2 ainda não aprovado pela FDA na DA, completou ECR de fase 2 e 3 em combinação com corticosteroides tópicos em adultos com DA moderada a grave. Na semana 16, o baricitinibe 4mg proporcionou melhora de 54,9% e 59,4% no escore EASI no BREEZE‐AD1 e BREEZE‐AD2, respectivamente.<a class="elsevierStyleCrossRef" href="#bib1095">61</a>Tezepelumabe é mAb humano que se liga à linfopoietina estromal do timo (TSLP, citocina derivada de células epiteliais que induz a produção de citocinas Th2, incluindo IL‐4, IL‐5 e IL‐13)<a class="elsevierStyleCrossRef" href="#bib1100">62</a> usado no tratamento da asma. Ele foi testado em doses de 280mg a cada duas semanas em estudos de fase 2, alcançando escore EASI‐50 em 65% dos pacientes na 12ª semana de tratamento.<a class="elsevierStyleCrossRef" href="#bib1105">63</a> Fezaquinumabe, mAb humano contra IL‐22, está em estudos de fase 2. Doses de indução de 600mg seguidas de 300mg a cada duas semanas demonstraram melhora no escore IGA a partir de 12 semanas de uso.<a class="elsevierStyleCrossRef" href="#bib1110">64</a> Nemolizumabe é mAb anti‐IL‐31RA experimentado em estudos de fase 2. Foi relatado que 42% dos pacientes tratados apresentaram melhora no escore EASI após 12 semanas de uso.<a class="elsevierStyleCrossRef" href="#bib1115">65</a> O etoquimabe é outro mAb experimental que se liga à IL‐33 em fase inicial de desenvolvimento. No momento, os estudos testaram doses de 300mg IV uma vez, alcançando escore EASI‐50 em 100% dos participantes em 140 dias.<a class="elsevierStyleCrossRef" href="#bib1120">66</a>Novas terapias imunológicas tópicas direcionadas para DA apareceram recentemente como ferramentas terapêuticas. O creme de ruxolitinibe 1,5% (aprovado pela FDA em 2021) para pacientes >12 anos mostra melhora de 71,6% no escore EASI após quatro semanas de uso.<a class="elsevierStyleCrossRef" href="#bib1125">67</a> O creme de tofacitinibe 2% mostrou melhora de 82% no escore EASI após quatro semanas de uso e está aguardando a aprovação da FDA.<a class="elsevierStyleCrossRefs" href="#bib1130">68,69</a>Perfil de segurança da imunoterapia direcionada para DAOs EA mais comuns foram infecções do trato respiratório superior e reações no local da injeção para todas as classes.<a class="elsevierStyleCrossRefs" href="#bib1010">44,45</a> Considerações gerais devem ser observadas em relação à reativação de tuberculose, hepatite B e, no caso de JAKis, considerar também infecções por membros da família Herpesvírus.<a class="elsevierStyleCrossRefs" href="#bib1080">58,60</a> Outros EA comuns em todas as classes foram sintomas oculares (conjuntivite, ceratite, blefarite, prurido ocular, ressecamento e desconforto ocular). Dupilumabe e traloquinumabe não requerem monitoramento laboratorial, mas abrocitinibe, baricitinibe e upadacitinibe necessitam de seguimento laboratorial. Eles podem induzir elevação da creatinofosfoquinase, trombocitopenia e neutropenia.<a class="elsevierStyleCrossRef" href="#bib1015">45</a> Outros EA relatados para JAKis são náusea, cefaleia, diarreia, fadiga, acne, dor abdominal e mialgias.<a class="elsevierStyleCrossRef" href="#bib1140">70</a>Recentemente, observou‐se risco aumentado de artrite inflamatória soronegativa e psoríase em pacientes em uso de dupilumabe.<a class="elsevierStyleCrossRef" href="#bib1145">71</a> Com base nas evidências atuais, parece que o uso de anti‐TNF‐α para psoríase e anti‐IL‐4/13 para DA estão inversamente relacionados. O bloqueio duplo com dupilumabe está associado a doenças psoriasiformes, enquanto medicamentos biológicos para psoríase podem causar mudança fenotípica para eczema.<a class="elsevierStyleCrossRef" href="#bib1150">72</a>Para produtos tópicos, irritação local leve foi o EA mais comum.<a class="elsevierStyleCrossRefs" href="#bib1125">67,68</a>Não existem dados suficientes para determinar se qualquer terapia imunológica direcionada é mais segura do que outra para a DA. O abrocitinibe, 100mg/dia, foi associado a 2,6 vezes mais chances de EA graves em comparação com dupilumabe, mas com doses mais altas (isto é, abrocitinibe, 200mg/dia) as chances foram menores (1,4).<a class="elsevierStyleCrossRef" href="#bib1010">44</a>Taxas mais baixas de EA graves foram observadas com dupilumabe em comparação com placebo.<a class="elsevierStyleCrossRef" href="#bib1010">44</a> Dupilumabe também está associado a aumento não significante na infecção por herpes. A razão para a diminuição de infecções cutâneas, incluindo eczema herpético, é desconhecida, mas a melhora na barreira cutânea e no microbioma causada pela imunoterapia direcionada pode explicar essa observação.<a class="elsevierStyleCrossRef" href="#bib1155">73</a>Hidradenite supurativaA hidradenite supurativa (HS) é doença autoinflamatória do folículo pilossebáceo com prevalência variando de 0,05%‐4,1%.<a class="elsevierStyleCrossRef" href="#bib1160">74</a> Existem pelo menos nove diretrizes clínicas que consideram o uso de produtos biológicos no manejo da HS.<a class="elsevierStyleCrossRefs" href="#bib1165">75–83</a>Critérios de eligibilidadeO manejo com imunoterapia direcionada deve ser considerado precocemente em casos graves. As diretrizes internacionais recomendam iniciar tratamento direcionado para HS recalcitrante moderada a grave, definida como estágio II‐III de Hurley, ou contagem total de abcessos e nódulos inflamatórios ≥ 3 no início do estudo e resposta inadequada ao tratamento com antibióticos orais por pelo menos 90 dias.TerapiaExistem poucas terapias direcionadas para HS que devem ser selecionadas de acordo com diferentes critérios clínicos em cada paciente (<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>). O adalimumabe<a class="elsevierStyleCrossRef" href="#bib1210">84</a> é o único tratamento biológico aprovado pela FDA para HS (2015) e é recomendado como medicamento biológico de primeira linha em todas as diretrizes; o infliximabe é a segunda opção.<a class="elsevierStyleCrossRef" href="#bib1160">74</a> Anakinra e bermequimabe podem ser considerados após falha dos agentes anti‐TNF‐α, mas as evidências que apoiam sua eficácia na HS são limitadas.<a class="elsevierStyleCrossRef" href="#bib1160">74</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>O adalimumabe mostrou melhora de 41,8% a 58,9% na resposta clínica à HS (HiSCR, Hidradenitis Suppurativa Clinical Response) em 50% dos pacientes em 12 semanas.<a class="elsevierStyleCrossRef" href="#bib1210">84</a> O infliximabe demonstrou melhora de 25%‐50% no Hidradenitis Suppurativa Severity Index (HSSI) em 60% dos pacientes em oito semanas.<a class="elsevierStyleCrossRef" href="#bib1215">85</a> Outros anti‐TNFs não são utilizados para tratar a HS, como etanercepte ou golimumabe, em virtude de reações paradoxais de piora ou indução da doença.<a class="elsevierStyleCrossRefs" href="#bib1160">74,86</a>Os medicamentos anti‐IL‐1 comprovaram sua eficácia em pequenos ECR controlados por placebo.<a class="elsevierStyleCrossRefs" href="#bib1225">87,88</a> Anakinra mostrou melhora >50% no Disease Activity Score (DAS) em 78% dos pacientes em 12 semanas de tratamento.<a class="elsevierStyleCrossRef" href="#bib1225">87</a> O bermequimabe mostrou melhora de 60% no HiSCR em 12 semanas de tratamento.<a class="elsevierStyleCrossRef" href="#bib1230">88</a> Esses medicamentos devem ser considerados quando os pacientes não são candidatos à terapia anti‐TNF‐α.As diretrizes clínicas também mencionam outros produtos biológicos que têm sido utilizados com sucesso em séries de casos para o tratamento da HS (guselcumabe, risanquizumabe, secuquinumabe, bimequizumabe e upadacitinibe), mas os resultados em pacientes tratados com esses medicamentos baseiam‐se principalmente em relatos de casos isolados, o que não é suficiente para recomendar seu uso no ambiente clínico.<a class="elsevierStyleCrossRef" href="#bib1220">86</a>Perfil de segurança da imunoterapia direcionada para HSO perfil de segurança dos medicamentos anti‐TNF‐α foi discutido em seção anterior (ver Psoríase). Para os medicamentos anti‐IL‐1, as considerações gerais são semelhantes entre eles. Os EA mais comuns são reações no local da injeção e infecções do trato respiratório superior. Outros EA relatados são cefaleia, dor abdominal, diarreia e sintomas semelhantes aos da gripe.<a class="elsevierStyleCrossRef" href="#bib1235">89</a>Pioderma gangrenosoO pioderma gangrenoso (PG) é dermatose neutrofílica caracterizada por úlceras cutâneas crônicas e recorrentes com borda necrolítica, com incidência estimada de 3‐10/1.000.000 de casos por ano.<a class="elsevierStyleCrossRef" href="#bib1240">90</a> Atualmente, não existem medicamentos aprovados pela FDA para essa doença. Recentemente, novas terapias imunológicas direcionadas têm sido utilizadas com algum sucesso para tratar casos refratários de PG, mas ensaios clínicos são necessários para estabelecer a real eficácia dessas terapias.<a class="elsevierStyleCrossRefs" href="#bib1245">91–93</a>Critérios de eligibilidadeSugere‐se considerar a imunoterapia direcionada no PG após estudo completo para estabelecer o diagnóstico dessa condição.<a class="elsevierStyleCrossRef" href="#bib1260">94</a> A doença deve ser recalcitrante ou de intensidade moderada a grave (ASC >10%, locais anatômicos complexos ou dor excruciante).TerapiaExistem poucas terapias direcionadas para o PG que devem ser selecionadas de acordo com diferentes critérios clínicos em cada paciente (<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>). O medicamento com mais dados para o tratamento do PG é o infliximabe.<a class="elsevierStyleCrossRef" href="#bib1260">94</a> O infliximabe demonstrou melhora das lesões na quarta semana (20/29 pacientes), com remissão completa em 21% na sexta semana.<a class="elsevierStyleCrossRef" href="#bib1260">94</a> O infliximabe também tem sido utilizado com sucesso em combinação com outros medicamentos (corticosteroides sistêmicos orais, azatioprina, micofenolato de mofetil e ciclosporina).<a class="elsevierStyleCrossRefs" href="#bib1250">92,93,95</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Há relatos de casos de PG tratados com adalimumabe e etanercepte.<a class="elsevierStyleCrossRef" href="#bib1265">95</a> Com base nesses dados observacionais, não foram encontradas diferenças significantes nas taxas de resposta parcial ou completa ao infliximabe, adalimumabe e etanercepte. Em uma revisão semissistemática sobre inibidores de TNF‐α, foi encontrada taxa de resposta parcial de 87% e resposta completa de 67%.<a class="elsevierStyleCrossRef" href="#bib1265">95</a> O corticosteroide e a ciclosporina podem atingir 90% de taxa de resposta parcial e apenas 47% de taxa de resposta completa após seis meses.<a class="elsevierStyleCrossRef" href="#bib1265">95</a>Medicamentos anti‐IL‐1 também têm sido utilizados para tratar PG.<a class="elsevierStyleCrossRef" href="#bib1245">91</a> Há 29 casos relatados na literatura do uso de anakinra em pacientes com comorbidades como artrite reumatoide, psoríase e síndromes PASH (pioderma gangrenoso, acne e hidradenite supurativa) e PAPA (artrite piogênica, pioderma gangrenoso e acne) na dose de 100mg/dia.<a class="elsevierStyleCrossRefs" href="#bib1245">91,92</a> Em um ensaio não controlado, canaquinumabe foi usado em cinco pacientes com PG refratário a esteroides. Quatro mostraram redução no tamanho da lesão‐alvo e três alcançaram remissão completa.<a class="elsevierStyleCrossRef" href="#bib1270">96</a>Outras terapias imunológicas direcionadas usadas com sucesso são ustequinumabe (anti‐IL‐12/23)<a class="elsevierStyleCrossRef" href="#bib1275">97</a> e ruxolitinibe (anti‐JAK1‐2).<a class="elsevierStyleCrossRefs" href="#bib1245">91,92</a>Perfil de segurança da imunoterapia direcionada para PGHá casos relatados de indução paradoxal de PG com o uso de adalimumabe, etanercepte e, em menor número, com infliximabe.<a class="elsevierStyleCrossRef" href="#bib1240">90</a>As reações adversas específicas do canaquinumabe são piora da artrite reumatoide, pirexia, vômitos, sinusite e artralgia e, para anakinra, ganho ponderal, dor musculoesquelética e vertigem.<a class="elsevierStyleCrossRef" href="#bib1270">96</a>Urticária espontânea crônicaA urticária espontânea crônica (UEC) é definida pelo aparecimento de pápulas pruriginosas transitórias e/ou angioedema por pelo menos seis semanas sem um gatilho reconhecível.<a class="elsevierStyleCrossRef" href="#bib1280">98</a> A prevalência global de UEC é de 1,1%, de acordo com a Global Burden of Disease.<a class="elsevierStyleCrossRef" href="#bib1285">99</a>Critérios de eligibilidadeAdultos e adolescentes com 12 anos ou mais podem ser considerados para terapia imunológica direcionada se permanecerem sintomáticos apesar do tratamento com anti‐histamínicos H1 até quatro vezes a dose padrão, ou se persistirem sintomáticos com a terapia combinada (anti‐histamínicos H1 quatro vezes a dose padrão mais anti‐histamínicos H2 e/ou antagonista do receptor de leucotrieno).<a class="elsevierStyleCrossRefs" href="#bib1280">98,100</a>TerapiaExiste apenas uma imunoterapia direcionada atualmente aprovada para UEC, e outras opções devem ser selecionadas em casos refratários ou no contexto de pesquisa (<a class="elsevierStyleCrossRef" href="#tbl0025">tabela 5</a>). O omalizumabe, um mAb anti‐IgE, foi aprovado pela FDA em 2014 para uso em pacientes >12 anos com UEC. Essa autorização foi baseada em dois ECRs (ASTERIA I e ASTERIA II).<a class="elsevierStyleCrossRef" href="#bib1295">101</a> ECRs mostraram que, em 40 semanas, 75,3% dos pacientes com UEC obtiveram resposta completa e 14,6% tiveram resposta parcial.<a class="elsevierStyleCrossRef" href="#bib1300">102</a><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>O ligelizumabe, um mAb anti‐IgE, ainda está em estudo, mas ensaios clínicos recentes para o tratamento da UEC estão mostrando eficácia semelhante ao omalizumabe.<a class="elsevierStyleCrossRefs" href="#bib1305">103,104</a>Lirentelimabe é mAb de lectina 8 semelhante à imunoglobulina com ligação ao ácido antissiálico (anti‐SIGLEC‐8, um receptor inibitório presente em eosinófilos e mastócitos). A ligação ao SIGLEC‐8 induz a morte de eosinófilos, inibe a degranulação mediada por IgE dos mastócitos e a síntese de novo de prostaglandina D2. Os resultados de um estudo de fase 2 com lirentelimabe para o tratamento de UEC e para o tratamento de urticária induzível demonstraram 92% de resposta completa na semana 22 e apenas 36% de resposta completa em pacientes anteriormente refratários ao tratamento com omalizumabe.<a class="elsevierStyleCrossRef" href="#bib1315">105</a>O dupilumabe demonstrou resposta parcial em relatos de casos.<a class="elsevierStyleCrossRef" href="#bib1320">106</a> Benralizumabe e mepolizumabe, ambas moléculas experimentais anti‐IL‐5R e anti‐IL‐5, respectivamente, também foram utilizados.<a class="elsevierStyleCrossRef" href="#bib1325">107</a> Em ambos os casos, os pacientes tratados apresentaram melhora clínica.<a class="elsevierStyleCrossRef" href="#bib1330">108</a> O secuquinumabe tem sido usado em relatos de casos para o tratamento de UEC em pacientes refratários ao tratamento com anti‐histamínicos H1 e omalizumabe, mostrando redução significante na atividade da doença desde o início.<a class="elsevierStyleCrossRef" href="#bib1335">109</a>Perfil de segurança da imunoterapia direcionada para UECOs efeitos adversos mais comuns, mas controláveis, do omalizumabe são cefaleia, dor abdominal superior, pirexia e reação local no local da injeção. Efeitos adversos mais graves, como reação anafilática, síncope e angioedema, foram relatados com frequência inferior a 1/1.000.<a class="elsevierStyleCrossRef" href="#bib1280">98</a>Para o lirentelimabe, os EA mais comuns incluíram reações relacionadas à infusão, nasofaringite e cefaleia. Não ocorreram EA graves relacionados ao tratamento.<a class="elsevierStyleCrossRef" href="#bib1315">105</a>Alopecia areataAlopecia areata (AA) é doença autoimune decorrente da perda do privilégio imunológico do folículo piloso. Recentemente, a FDA aprovou o baricitinibe para tratamento de AA (2022) e muitos outros JAKis estão em estudo avançado para aprovação.Critérios de eligibilidadeOs pacientes devem ser considerados para tratamento com JAKis se tiverem doença moderada ou grave (perda total de cabelos ≥ 30% do couro cabeludo por pelo menos três a seis meses, medida utilizando o escore da ferramenta Severity of Alopecia Tool [SALT] ou resposta refratária ao tratamento convencional nos últimos seis meses). Não há limitação quanto à duração anterior da alopecia e os estudos consideraram pacientes com ampla variação de duração da AA como candidatos ao tratamento com JAKis.<a class="elsevierStyleCrossRefs" href="#bib1340">110,111</a>TerapiaExiste apenas uma imunoterapia direcionada atualmente aprovada para AA, mas outras opções têm sido utilizadas com sucesso e devem ser selecionadas de acordo com diferentes critérios clínicos em cada paciente (<a class="elsevierStyleCrossRef" href="#tbl0030">tabela 6</a>). A FDA aprovou o baricitinibe (2022), um JAK 1‐2i, para o tratamento de AA em adultos. Sua eficácia foi avaliada em dois ensaios randomizados, duplo‐cegos e controlados por placebo (BRAVE AA‐1 e BRAVE AA‐2).<a class="elsevierStyleCrossRef" href="#bib1340">110</a> Os pacientes nesses estudos receberam 2 ou 4mg de baricitinibe por dia. Os resultados finais na semana 36 mostraram resposta adequada de 22% com 2mg e 38% com 4mg Resultados semelhantes foram observados no BRAVE AA‐2 (19% de resposta adequada com 2mg e 35% com 4mg).<a class="elsevierStyleCrossRef" href="#bib1340">110</a> Tofacitinibe, um JAK 1‐3i, tem sido usado para tratar casos moderados a graves de AA com >50% de perda de cabelo no couro cabeludo em adultos, alcançando resposta completa em 20% dos pacientes tratados e 77% de resposta parcial em quatro a 18 meses de tratamento.<a class="elsevierStyleCrossRef" href="#bib1350">112</a> Em 2023, a FDA aprovou o ritlecitinibe para o tratamento da AA em pessoas com mais de 12 anos com base nos resultados do estudo ALLEGRO, no qual 23% dos pacientes alcançaram recuperação capilar de pelo menos 80% após seis meses de tratamento.<a class="elsevierStyleCrossRef" href="#bib1355">113</a> Ruxolitinibe é o último JAKi usado para o tratamento da AA, atingindo de forma geral resposta em 93% dos pacientes e resposta completa em 21% dos pacientes tratados em seis meses de seguimento.<a class="elsevierStyleCrossRef" href="#bib1345">111</a><elsevierMultimedia ident="tbl0030"></elsevierMultimedia>Perfil de segurança da imunoterapia direcionada para AAO perfil de segurança dos medicamentos inibidores de JAK foi extensivamente estudado e, em geral, todos os JAKis utilizados para o tratamento de AA são bem tolerados. Infecções do trato respiratório superior, hipercolesterolemia, creatina fosfoquinase elevada, cefaleia, diarreia e nasofaringite são os EA relatados com mais frequência. Os efeitos adversos menos comuns incluíram outras infecções, como herpes‐zóster, herpes‐simples, infecções do trato urinário e gastroenterite.<a class="elsevierStyleCrossRefs" href="#bib1340">110–112</a>Doenças bolhosas autoimunesAs doenças bolhosas autoimunes são um grupo de doenças caracterizadas pela produção de autoanticorpos contra moléculas de adesão da pele.<a class="elsevierStyleCrossRef" href="#bib1360">114</a> Essa revisão irá discutir a imunoterapia direcionada para pênfigo vulgar (PV), pênfigo foliáceo (PF) e penfigoide bolhoso (PB).Critérios de eligibilidadeOs pacientes são candidatos à imunoterapia direcionada como opção de primeira linha em casos de PV/PF moderado a grave de início recente ou em pacientes previamente tratados que não alcançam remissão clínica com corticosteroides sistêmicos ou adjuvantes imunossupressores.<a class="elsevierStyleCrossRef" href="#bib1360">114</a> A gravidade da doença deve ser medida por meio do escore do Pemphigus Disease and Area Index (PDAI). O envolvimento múltiplo das mucosas (oral, nasofaríngea, conjuntival, genital) ou PDAI ≥15 são considerados doença moderada. Pacientes com escore PDAI ≥45 ou lesões orais, disfagia e perda ponderal apresentam doença grave.<a class="elsevierStyleCrossRefs" href="#bib1365">115,116</a>TerapiaO rituximabe é o único medicamento biológico aprovado pela FDA (2018) para doenças bolhosas e é considerado a primeira opção terapêutica para PV e PF pelas diretrizes internacionais.<a class="elsevierStyleCrossRef" href="#bib1370">116</a> Essa aprovação foi baseada nos resultados do Rituxi3,<a class="elsevierStyleCrossRef" href="#bib1365">115</a> no qual 89% dos pacientes com pênfigo tratados com rituximabe e prednisolona oral estavam livres da doença e sem necessidade de qualquer tratamento adicional após 24 meses, em comparação com 34% com prednisolona isoladamente. O tratamento com rituximabe também reduziu a dose de corticosteroides necessária para a remissão clínica, reduzindo os efeitos adversos associados a altas doses de esteroides<a class="elsevierStyleCrossRef" href="#bib1375">117</a> (<a class="elsevierStyleCrossRef" href="#tbl0035">tabela 7</a>).<elsevierMultimedia ident="tbl0035"></elsevierMultimedia>Efgartigimode é anticorpo IgG1 humano direcionado ao receptor Fc neonatal. O bloqueio do receptor Fc neonatal diminui a disponibilidade de anticorpos IgG patogênicos e foi testado para o tratamento de PF e PV.<a class="elsevierStyleCrossRef" href="#bib1380">118</a> Em um ensaio de fase 2, a utilização isolada de efgartigimode demonstrou controle precoce da doença em 90% dos pacientes após 17 dias. Combinado com prednisona, levou à remissão clínica completa em 64% dos pacientes após seis meses.<a class="elsevierStyleCrossRef" href="#bib1385">119</a> Dois ensaios clínicos de fase 3 avaliando a eficácia e a segurança do efgartigimode em adultos com pênfigo (<a href="ctgov:NCT04598451">NCT04598451</a> e <a href="ctgov:NCT04598477">NCT04598477</a>) estão em andamento.<a class="elsevierStyleCrossRef" href="#bib1375">117</a>O fator de ativação de células B (BAFF), também conhecido como estimulador de linfócitos B (BLyS), é um importante ativador de células B.<a class="elsevierStyleCrossRef" href="#bib1390">120</a> O ianalumabe é um mAb experimental que se liga ao BLyS. Um ensaio clínico de fase 2 foi conduzido para determinar as doses, o benefício e a segurança do ianalumabe em pacientes com PV, mostrando diminuição de 73% no escore médio do PDAI na semana 12 em sete pacientes com pênfigo em comparação com controles tratados com placebo.<a class="elsevierStyleCrossRef" href="#bib1395">121</a>Tratamento com rituximabe, omalizumabe e dupilumabe está relatado em pacientes com PB. Cao et al.<a class="elsevierStyleCrossRef" href="#bib1400">122</a> conduziram uma revisão sistemática para avaliar o uso desses três produtos biológicos em pacientes com PB refratários ao uso de outras terapias sistêmicas, como corticosteroides sistêmicos, metotrexato, micofenolato de mofetil, azatioprina, ciclosporina e ciclofosfamida. Os autores descobriram que o rituximabe levou à remissão completa em 70,5% e à remissão parcial em 23,8% dos pacientes após seis meses de seguimento, com taxa de recorrência de 20,5%.<a class="elsevierStyleCrossRef" href="#bib1400">122</a> O omalizumabe levou à remissão completa em 67,9% e à remissão parcial em 20,8% dos pacientes em seis meses, com taxa de recorrência de 5,7%.<a class="elsevierStyleCrossRef" href="#bib1400">122</a> O dupilumabe levou à remissão completa em 66,7% e à remissão parcial em 19,4% dos pacientes após 4,5 meses de tratamento, com taxa de recorrência de 5,6%.<a class="elsevierStyleCrossRefs" href="#bib1405">123,124</a>Perfil de segurança da imunoterapia direcionada para doenças bolhosasEmbora o rituximabe seja um excelente medicamento para PV ou PF graves, ele também está associado a EA graves bem conhecidos. Os mais bem documentados são reações à infusão, infecções, distúrbios cardíacos e casos de leucoencefalopatia multifocal progressiva fatal.<a class="elsevierStyleCrossRef" href="#bib1360">114</a> A maioria desses EA pode ser controlada clinicamente se forem reconhecidos no estágio inicial.Um estudo recente mostrou que o tratamento com rituximabe foi associado a menor risco de desenvolvimento de comorbidades cardiovasculares e metabólicas, por isso pode ser particularmente preferido em indivíduos com fatores de risco cardiovasculares e metabólicos, para os quais os EA relacionados aos corticosteroides devem ser rigorosamente evitados.<a class="elsevierStyleCrossRef" href="#bib1415">125</a>Outras doenças dermatológicasSerão consideradas nesta seção doenças com evidências escassas (pequenos ensaios ou séries de casos, evidências indiretas de outras doenças ou ensaios em andamento sem resultados) ou com terapia tópica, mas sem terapia sistêmica disponível (<a class="elsevierStyleCrossRef" href="#tbl0040">tabela 8</a>).<elsevierMultimedia ident="tbl0040"></elsevierMultimedia>Síndrome de Stevens‐Johnson/necrólise epidérmica tóxicaA síndrome de Stevens‐Johnson/necrólise epidérmica tóxica (SSJ/NET) é doença mucocutânea grave e rara causada pela exposição a determinados medicamentos – os mais frequentes são sulfonamidas, anticonvulsivantes, anti‐inflamatórios não esteroides, alopurinol e penicilinas.<a class="elsevierStyleCrossRef" href="#bib1420">126</a> Em virtude de sua baixa incidência, o uso relatado de produtos biológicos nessa doença foi limitado principalmente a séries de casos e apenas dois ensaios.<a class="elsevierStyleCrossRefs" href="#bib1420">126–128</a> Com os dados atuais, a eficácia e a segurança da monoterapia biológica e da terapia combinada não podem ser determinadas de maneira conclusiva, e o papel final desses medicamentos ainda está sendo pesquisado.O maior número de casos relatados está relacionado com o etanercepte. O regime terapêutico mais utilizado é 25mg (em crianças com peso <65kg) e 50mg (adultos ou crianças >65kg) nos dias 0 e 3. A monoterapia com etanercepte alcançou reepitelização em 13 dias e taxa de mortalidade de 7,6%, enquanto os pacientes tratados com etanercepte em combinação com corticosteroides alcançaram reepitelização em 11,1 dias e tiveram taxa de mortalidade de 7,7%.<a class="elsevierStyleCrossRef" href="#bib1420">126</a> Wang et al.<a class="elsevierStyleCrossRef" href="#bib1425">127</a> conduziram um ECR no qual 96 pacientes com SSJ/NET foram incluídos para comparar os efeitos do etanercepte aos corticosteroides tradicionais. O estudo demonstrou que o etanercepte diminuiu a mortalidade prevista com base no escore de gravidade específico para NET (SCORTEN) em cerca de 9,4% em comparação aos corticosteroides tradicionais.<a class="elsevierStyleCrossRef" href="#bib1425">127</a> O infliximabe geralmente era usado na dose de 5mg/kg.<a class="elsevierStyleCrossRef" href="#bib1420">126</a> Em relatos de casos de pacientes tratados com infliximabe em monoterapia, o número médio de dias até a reepitelização foi de 10,4 e não houve relatos de mortalidade.<a class="elsevierStyleCrossRef" href="#bib1420">126</a> Nos relatos de casos de NET tratados com a combinação infliximabe/corticosteroides sistêmicos, o número médio de dias para reepitelização foi de 14,2 e a taxa média de mortalidade foi de 22,2%. Uma revisão Cochrane recente mostrou que o etanercepte 25mg (50mg se >65kg) duas vezes por semana até a cicatrização das lesões cutâneas pode reduzir a mortalidade específica da doença em comparação com os corticosteroides (RR=0,51; IC95% 0,16‐1,63). com possíveis benefícios e possíveis danos.<a class="elsevierStyleCrossRef" href="#bib1435">129</a>Em relação ao uso de imunoterapia direcionada utilizada na SSJ/NET em comparação aos corticosteroides, não houve diferença estatística observada entre os dois grupos de tratamento na incidência de EA; entretanto, houve menor incidência de hemorragia gastrintestinal relatada com produtos biológicos versus corticosteroide tradicional.<a class="elsevierStyleCrossRefs" href="#bib1420">126,127,130</a>DiHS/DRESSA síndrome de hipersensibilidade induzida por medicamentos/reação a medicamentos com eosinofilia e sintomas sistêmicos (DiHS/DRESS) é uma reação medicamentosa grave com mortalidade de 10%.<a class="elsevierStyleCrossRef" href="#bib1445">131</a> Casos de sucesso foram publicados usando terapia imunológica direcionada. Em um relato recente estudando dois casos de DRESS associado a envolvimento miocárdico, tofacitinibe 5mg duas vezes ao dia foi usado (por três anos) sequencialmente associado a corticosteroides, ciclosporina, metotrexato ou IVIg.<a class="elsevierStyleCrossRef" href="#bib1450">132</a> Os dois casos demonstraram remissão quando o tofacitinibe foi utilizado.<a class="elsevierStyleCrossRef" href="#bib1450">132</a>Um estudo relato de casos anterior de 10 pacientes com DRESS demonstrou tempo médio de cicatrização de 8,5 dias após injeção subcutânea de 50mg de etanercepte.<a class="elsevierStyleCrossRef" href="#bib1445">131</a> Por fim, há um único relato de caso de paciente tratado com sucesso com mepolizumabe.<a class="elsevierStyleCrossRef" href="#bib1455">133</a>Líquen planoO adalimumabe é a única imunoterapia direcionada recomendada pelas diretrizes internacionais para o tratamento de LP cutâneo e mucoso, em casos refratários graves.<a class="elsevierStyleCrossRef" href="#bib1460">134</a> Seu uso melhora o prurido e obtém a cicatrização das lesões cutâneas em um período de seis meses.<a class="elsevierStyleCrossRef" href="#bib1460">134</a> Outra imunoterapia direcionada para LP é o ruxolitinibe tópico, que está em estudos de fase 2 para tratar LP cutâneo.<a class="elsevierStyleCrossRef" href="#bib1465">135</a> Ele foi testado como creme a 1,5% duas vezes ao dia, mostrando melhora no escore clínico e escore modificado do Composite Assessment of Index Lesion Severity (mCAILS) após quatro semanas de tratamento.<a class="elsevierStyleCrossRef" href="#bib1465">135</a> O uso de tofacitinibe foi relatado em séries de casos em doses de 5mg (duas vezes ao dia) em períodos de seguimento variando de dois a nove meses para tratar líquen plano pilar (LPP) e LP hipertrófico, mostrando melhora clínica e no escore LPP Activity Index (LPPAI).<a class="elsevierStyleCrossRef" href="#bib1470">136</a> O relato do uso de outros JAKis, como upadacitinibe ou baricitinibe, é escasso. Há 13 pacientes relatados em séries de casos e relatos de casos usando baricitinibe para LPP, com cinco alcançando resolução parcial, sete sem resolução e apenas um com resolução completa. Há apenas dois relatos de caso com o uso de upadacitinibe para LP, e ambos obtiveram resolução completa.<a class="elsevierStyleCrossRef" href="#bib1475">137</a> Por fim, estudos de fase 2 estão sendo realizados atualmente com ixequizumabe (LP cutâneo, LPP) e secuquinumabe (LP cutâneo, LPP e LP oral).<a class="elsevierStyleCrossRef" href="#bib1480">138</a>Lúpus eritematoso cutâneoA FDA aprovou o anifrolumabe para o lúpus eritematoso sistêmico (LES) em julho de 2021.<a class="elsevierStyleCrossRef" href="#bib1485">139</a> O anifrolumabe é anticorpo monoclonal totalmente humanizado que inibe seletivamente o receptor 1 do IFN‐α.<a class="elsevierStyleCrossRef" href="#bib1485">139</a> No ECR TULIP‐2, o anifrolumabe foi testado para o tratamento do LES, em pacientes com doença cutânea pelo menos moderadamente grave, e 49% dos pacientes obtiveram redução no escore Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) ≥ 50% em comparação com 25% no grupo placebo.<a class="elsevierStyleCrossRef" href="#bib1490">140</a> O belimumabe é outro medicamento aprovado pela FDA em 2011 para tratamento do LES. Ainda não há resultados finais específicos para a pele em relação a esse medicamento no LEC.<a class="elsevierStyleCrossRef" href="#bib1495">141</a>VitiligoPara o vitiligo, o ruxolitinibe tópico foi aprovado pela FDA em 2022 para o tratamento de doença não segmentar comprometendo <10% da ASC em pacientes adultos e pediátricos com >12 anos. Em dois ensaios de fase 3 (TRuE‐V1 e TRuE‐V2), os indivíduos foram randomizados para tratamento com ruxolitinibe creme a 1,5% ou placebo duas vezes ao dia durante duas semanas. No final do período de tratamento de 24 semanas, 30% dos pacientes que receberam ruxolitinibe tiveram pelo menos 75% de melhora no Vitiligo Area Scoring Index (VASI) facial, em comparação com 10% dos pacientes que receberam placebo.<a class="elsevierStyleCrossRef" href="#bib1500">142</a> Também nesses estudos, o creme de ruxolitinibe mostrou melhora na pigmentação acral, o que historicamente tem sido uma área refratária à repigmentação com fototerapia, corticosteroides tópicos e tacrolimus.<a class="elsevierStyleCrossRef" href="#bib1500">142</a> Um estudo piloto com 11 pacientes com vitiligo facial usando creme de tofacitinibe 2% em conjunto com UVB de banda estreita mostrou redução de 70% no escore VASI após dois a quatro meses.<a class="elsevierStyleCrossRef" href="#bib1505">143</a> Por outro lado, uma série de casos de 10 pacientes em uso de tofacitinibe 5mg duas vezes ao dia por 10 meses e UVB de banda estreita ou fotoexposição obteve diminuição de apenas 5,4% na ASC (cinco pacientes) e outros cinco pacientes não alcançaram qualquer repigmentação.<a class="elsevierStyleCrossRef" href="#bib1510">144</a>Doenças granulomatosas cutâneas (granuloma anular e sarcoidose)As doenças granulomatosas podem representar desafios terapêuticos. O manejo pode ser insatisfatório com a terapia sistêmica convencional.<a class="elsevierStyleCrossRef" href="#bib1515">145</a> O tratamento com anti‐TNF foi tentado com resultados variáveis.<a class="elsevierStyleCrossRef" href="#bib1520">146</a> A imunoterapia direcionada para JAKis parece ser opção promissora com base nos resultados de séries de casos recentes.<a class="elsevierStyleCrossRef" href="#bib1525">147</a> Tofacitinibe 5mg duas vezes ao dia foi utilizado em pacientes que não responderam aos corticosteroides. Em relato de casos de apenas um paciente, a remissão completa foi obtida após quatro meses de tratamento. Para sarcoidose (três pacientes), a mesma série de casos mostrou resposta completa em dois pacientes e melhora de 96% em um paciente.<a class="elsevierStyleCrossRef" href="#bib1525">147</a> Mais ECRs são necessários para estabelecer o valor real dos JAKis nas doenças granulomatosas.Síndrome hipereosinofílicaUma série de casos de cinco pacientes refratários a esteroides tratados com tofacitinibe 5mg duas vezes ao dia mostrou remissão completa em três deles e remissão quase completa em outro.<a class="elsevierStyleCrossRef" href="#bib1530">148</a> O paciente restante não conseguiu completar o tratamento com tofacitinibe por motivos relacionados ao seguro de saúde, e o tratamento foi alterado para ruxolitinibe 25mg pela manhã e 10mg à noite. Esse paciente também obteve remissão completa.<a class="elsevierStyleCrossRef" href="#bib1530">148</a>MorfeiaHá casos de sucesso com uso de imunoterapia direcionada para casos refratários de morfeia. Em dois pacientes com morfeia profunda generalizada associada à fasciíte eosinofílica que não responderam à corticoterapia, tofacitinibe (10mg duas vezes ao dia) foi adicionado à fototerapia e ao metotrexato, proporcionando melhora clínica em ambos.<a class="elsevierStyleCrossRef" href="#bib1535">149</a> Foi relatado que tocilizumabe (um medicamento anti‐IL‐6) é eficaz no tratamento da morfeia panesclerótica.<a class="elsevierStyleCrossRefs" href="#bib1540">150,151</a> Uma adolescente de 14 anos foi tratada com sucesso com infliximabe.<a class="elsevierStyleCrossRef" href="#bib1540">150</a>ConclusãoMuitas terapias imunológicas direcionadas são atualmente empregadas no tratamento de doenças dermatológicas inflamatórias. Algumas dessas moléculas ganharam papel importante no tratamento de doenças cutâneas crônicas e incapacitantes que não eram anteriormente controladas com tratamentos padrão, como o anti‐IL‐4/13 na DA, o anti‐TNF‐α na HS ou os inibidores de JAK na AA, gerando mudança de paradigma no arsenal terapêutico da dermatologia.<a class="elsevierStyleCrossRefs" href="#bib1010">44,152,153</a> Além disso, os avanços na compreensão da fisiopatologia dessas doenças facilitaram abordagens terapêuticas direcionadas para vias inflamatórias, como o bloqueio de citocinas dependentes de JAK‐STAT IL‐5, IL‐6, IL‐10 e IL‐13 em DiHS/DRESS.<a class="elsevierStyleCrossRef" href="#bib1450">132</a>Existem alguns aspectos críticos no desenvolvimento de terapias direcionadas para doenças inflamatórias da pele que devem ser considerados. A segurança em longo prazo é um aspecto relevante de todos os novos medicamentos. Alguns EA podem permanecer latentes durante os ensaios clínicos, aparecendo apenas com o uso prolongado. Outros – em muito poucos pacientes – podem surgir desde o início do tratamento, induzindo uma reação paradoxal com piora do quadro clínico sob tratamento com imunoterapia direcionada (p. ex., PG, psoríase).<a class="elsevierStyleCrossRefs" href="#bib0960">34,35,90</a> A colaboração entre agências reguladoras, profissionais de saúde e indústria farmacêutica é essencial na vigilância pós‐comercialização e nos estudos de seguimento de longo prazo para avaliar a segurança e a eficácia desses novos medicamentos.<a class="elsevierStyleCrossRef" href="#bib1560">154</a>Para que um medicamento seja considerado viável, ele deve garantir resultados clínicos superiores em comparação com os tratamentos existentes. Isso levou os estudos a utilizarem variáveis clinimétricas cada vez melhores (p. ex., PASI‐75 vs. PASI‐90 na psoríase),<a class="elsevierStyleCrossRef" href="#bib0850">12</a> mas não necessariamente a melhores comparações. Para comparar a eficácia entre medicamentos, os pesquisadores realizaram metanálises em rede, o que fornece algumas informações, mas tem suas limitações.<a class="elsevierStyleCrossRef" href="#bib1010">44</a> Essa dificuldade de comparação direta com os medicamentos antigos ocorre, por exemplo, no caso de JAKi versus metotrexato na DA moderada a grave, JAKi versus NB‐UVB no vitiligo e etanercepte versus prednisona na DRESS.<a class="elsevierStyleCrossRefs" href="#bib0880">18,44,133,142</a> Faltam estudos que avaliem o impacto econômico dessas decisões e que possam ajudar a aumentar o acesso a essas novas terapias.<a class="elsevierStyleCrossRef" href="#bib1565">155</a>Apesar da eficácia demonstrada em ensaios e estudos de evidências clínicas, as terapias direcionadas ainda são subutilizadas, especialmente em regiões de baixa ou média renda, em virtude da disponibilidade limitada e da cobertura de seguro inadequada. No Chile, por exemplo, 92% da população não têm cobertura para terapia direcionada para doenças cutâneas, o que leva a despesas pessoais.<a class="elsevierStyleCrossRef" href="#bib1570">156</a> Situação semelhante é observada no Peru, e condições ligeiramente melhores no Brasil.<a class="elsevierStyleCrossRef" href="#bib1570">156</a> Em uma pesquisa realizada pelo International Psoriasis Council em países com poucos recursos ou em desenvolvimento, incluindo Argentina, Brasil, Chile, Colômbia, México, Peru, China, Egito, Irã, Índia e África do Sul, os dermatologistas geralmente citaram o custo como a principal barreira ao acesso à terapia biológica para a psoríase.<a class="elsevierStyleCrossRef" href="#bib1575">157</a>A maioria das Diretrizes de Prática Clínica (DPC) para doenças inflamatórias da pele incorpora uma estratificação lógica do manejo médico em diferentes estágios da doença.<a class="elsevierStyleCrossRefs" href="#bib0930">28,45,75,100,116</a> Essa estratificação pode não refletir com precisão as condições sociossanitárias em várias regiões do mundo. A maioria (72,1%) das DPCs dermatológicas é originária de países com alto índice sociodemográfico (ISD), enquanto apenas uma pequena proporção vem de países de médio‐alto (8,0%), médio (5,3%) e baixo ISD (1,8%).<a class="elsevierStyleCrossRef" href="#bib1580">158</a> Geograficamente, a distribuição também não é uniforme, correspondendo a 51,8% na Europa, 21,2% na América do Norte, 15,5% na Ásia, 4,9% na América Latina e 4,4% na Australásia.<a class="elsevierStyleCrossRef" href="#bib1580">158</a> Assim, as DPCs adaptadas às necessidades regionais nos países em desenvolvimento ainda são escassas e necessárias para melhor manejo dos pacientes que utilizam terapia direcionada para doenças inflamatórias da pele.Esses novos moduladores imunológicos direcionados para o tratamento de doenças inflamatórias da pele estão passando pelas mesmas etapas históricas de desenvolvimento pelas quais muitos medicamentos importantes atualmente em uso passaram. Os dados apresentados e o elevado número de novos manuscritos que aparecem diariamente na literatura médica preveem um futuro promissor para a utilização desses medicamentos no tratamento de doenças crônicas da pele melhorando a qualidade de vida dos pacientes.Suporte financeiroNenhum.Contribuição dos autoresEdinson Lopez: Concepção e planejamento do estudo; obtenção, análise e interpretação dos dados; redação do manuscrito ou revisão crítica de conteúdo intelectual importante; revisão crítica da literatura; aprovação da versão final do manuscrito.Raul Cabrera: Concepção e planejamento do estudo; obtenção, análise e interpretação dos dados; redação do manuscrito ou revisão crítica de conteúdo intelectual importante; revisão crítica da literatura; aprovação da versão final do manuscrito.Cristóbal Lecaros: Concepção e planejamento do estudo; coleta, análise e interpretação dos dados; redação do manuscrito ou revisão crítica de conteúdo intelectual importante; revisão crítica da literatura; aprovação da versão final do manuscrito.Conflito de interessesNenhum." 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"sec0025" "titulo" => "Busca na literatura" ] 1 => array:3 [ "identificador" => "sec0030" "titulo" => "Psoríase" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Perfil de segurança da imunoterapia direcionada para psoríase" ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Populações especiais" ] ] ] 2 => array:3 [ "identificador" => "sec0055" "titulo" => "Dermatite atópica" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Critérios de elegibilidade" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Perfil de segurança da imunoterapia direcionada para DA" ] ] ] 3 => array:3 [ "identificador" => "sec0080" "titulo" => "Hidradenite supurativa" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Perfil de segurança da imunoterapia direcionada para HS" ] ] ] 4 => array:3 [ "identificador" => "sec0100" "titulo" => "Pioderma gangrenoso" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0110" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0115" "titulo" => "Perfil de segurança da imunoterapia direcionada para PG" ] ] ] 5 => array:3 [ "identificador" => "sec0120" "titulo" => "Urticária espontânea crônica" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0130" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0135" "titulo" => "Perfil de segurança da imunoterapia direcionada para UEC" ] ] ] 6 => array:3 [ "identificador" => "sec0140" "titulo" => "Alopecia areata" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0145" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0150" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0155" "titulo" => "Perfil de segurança da imunoterapia direcionada para AA" ] ] ] 7 => array:3 [ "identificador" => "sec0160" "titulo" => "Doenças bolhosas autoimunes" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0165" "titulo" => "Critérios de eligibilidade" ] 1 => array:2 [ "identificador" => "sec0170" "titulo" => "Terapia" ] 2 => array:2 [ "identificador" => "sec0175" "titulo" => "Perfil de segurança da imunoterapia direcionada para doenças bolhosas" ] ] ] 8 => array:3 [ "identificador" => "sec0180" "titulo" => "Outras doenças dermatológicas" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0185" "titulo" => "Síndrome de Stevens‐Johnson/necrólise epidérmica tóxica" ] 1 => array:2 [ "identificador" => "sec0190" "titulo" => "DiHS/DRESS" ] 2 => array:2 [ "identificador" => "sec0195" "titulo" => "Líquen plano" ] 3 => array:2 [ "identificador" => "sec0200" "titulo" => "Lúpus eritematoso cutâneo" ] 4 => array:2 [ "identificador" => "sec0205" "titulo" => "Vitiligo" ] 5 => array:2 [ "identificador" => "sec0210" "titulo" => "Doenças granulomatosas cutâneas (granuloma anular e sarcoidose)" ] 6 => array:2 [ "identificador" => "sec0215" "titulo" => "Síndrome hipereosinofílica" ] 7 => array:2 [ "identificador" => "sec0220" "titulo" => "Morfeia" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0225" "titulo" => "Conclusão" ] 6 => array:2 [ "identificador" => "sec0230" "titulo" => "Suporte financeiro" ] 7 => array:2 [ "identificador" => "sec0235" "titulo" => "Contribuição dos autores" ] 8 => array:2 [ "identificador" => "sec0240" "titulo" => "Conflito de interesses" ] 9 => array:1 [ "titulo" => "Referências" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-08-25" "fechaAceptado" => "2023-10-14" "PalabrasClave" => array:1 [ "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras‐chave" "identificador" => "xpalclavsec1834672" "palabras" => array:7 [ 0 => "Agentes de imunomodulação" 1 => "Dermatite atópica" 2 => "Dermatopatias" 3 => "Inibidores de Janus Quinases" 4 => "Produtos biológicos" 5 => "Psoríase" 6 => "Terapia de alvo molecular" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "FundamentosTerapias de alvo molecular, como anticorpos monoclonais (mAbs) e inibidores de Janus Quinase (JAKis), surgiram como ferramentas essenciais para o tratamento de doenças dermatológicas. Essas terapias modulam o sistema imune por vias de sinalização específicas, proporcionando alternativas eficazes aos agentes imunossupressores sistêmicos tradicionais. Esta revisão tem como objetivo fornecer um resumo atualizado das terapias imunológicas direcionadas para doenças inflamatórias da pele, considerando sua fisiopatologia, eficácia, dosagem e perfis de segurança. MétodosA revisão seguiu as diretrizes Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA). Uma busca sistemática foi conduzida na base de dados PubMed nos últimos 10 anos, com foco em ensaios clínicos randomizados, relatos de casos e séries de casos relacionados a terapias imunológicas direcionadas em dermatologia. Critérios de elegibilidade foram aplicados e os dados foram extraídos de cada estudo, incluindo dados de citações, desenho do estudo e resultados. ResultadosForam identificados 1.360 artigos não duplicados com a estratégia de busca inicial. A revisão do título e do resumo excluiu 1.150, enquanto a revisão do texto completo excluiu 50 artigos adicionais. A revisão incluiu 143 estudos publicados entre 2012 e 2022, destacando 39 medicamentos atualmente sob investigação ou em uso para o tratamento de doenças inflamatórias da pele. Limitações do estudoA heterogeneidade das informações resumidas limita esta revisão. Algumas recomendações originaram‐se de dados de ensaios clínicos, enquanto outras se basearam em análises retrospectivas e pequenas séries de casos. As recomendações provavelmente serão atualizadas à medida que novos resultados surgirem. ConclusãoAs terapias direcionadas revolucionaram o tratamento de doenças crônicas da pele, oferecendo novas opções para pacientes que não respondem aos tratamentos padrão. Reações paradoxais são raramente observadas. Mais estudos são necessários para compreender completamente os mecanismos e a natureza dessas terapias. Em geral, as terapias imunológicas direcionadas em dermatologia representam um desenvolvimento promissor, melhorando significantemente a qualidade de vida dos pacientes com doenças crônicas inflamatórias da pele." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Fundamentos" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Limitações do estudo" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusão" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Como citar este artigo: López E, Cabrera R, Lecaros C. Targeted therapy for immune mediated skin diseases. What should a dermatologist know? An Bras Dermatol. 2024;99:546–67." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "Trabalho realizado no Departamento de Dermatologia, Faculdade de Medicina, Universidad del Desarrollo‐Clínica Alemana de Santiago, Santiago, Chile." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Material suplementar" "identificador" => "sec0250" ] ] ] ] "multimedia" => array:11 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1519 "Ancho" => 3341 "Tamanyo" => 346358 ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas aprovadas pela FDA para doenças inflamatórias da pele." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2308 "Ancho" => 2508 "Tamanyo" => 339239 ] ] "descripcion" => array:1 [ "pt" => "Fluxograma PRISMA." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Tabela 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; VO, via oral; IV, intravenosa; a, anos; PASI, Psoriasis Area and Severity Index; ASC, área da superfície corporal; DLQI, Dermatology Life Quality Index." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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‐23 \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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‐IL‐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 indução: 150 mg semanas 0 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 150 mg a cada 12 semanas/SC \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‐IL‐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 indução: 100 mg semanas 0 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 100 mg a cada 8 semanas/SC \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‐IL‐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 indução: 100 mg semanas 0 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 100 mg a cada 12 semanas/SC \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‐17 \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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‐IL‐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 indução: 210 mg semanas 0, 1 e 2/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, BSA ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 210 mg a cada duas semanas/SC \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‐IL‐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 indução: 160 mg semana 0 SC, 80 mg semanas 2, 4, 6, 8, 10, 12/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, BSA ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 80 mg a cada quatro semanas/SC \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‐IL‐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 indução: 300 mg semanas 0,1,2,3 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 300 mg todos os meses/SC \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‐12/23 \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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‐IL‐12/23</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 indução: <100 kg: 45 mg semanas 0 e 4/SC; >100 kg: 90 mg semanas 0 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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: 42% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: <100 kg: 45 mg a cada 12 semanas/SC; >100 kg: 90 mg a cada 12 semanas/SC \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‐α \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 5 mg/kg semanas 0, 2 e 6/IV \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 5 mg/kg a cada oito semanas/IV \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 80 mg semana 0, 40 mg semana 1/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 40 mg a cada duas semanas/SC \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 400 mg semanas 0, 2 e 4/SC \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: <90 kg: 200 mg a cada duas semanas/SC; >90 kg: 400 mg a cada duas semanas/SC \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 200 mg na semana 0, 100 mg na semana 2 \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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% PASI‐75 semana 14<a class="elsevierStyleCrossRef" href="#bib0915">25</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 50 mg mg a cada quatro semanas/SC \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 50 mg duas vezes por semana/SC durante 12 semanas \t\t\t\t\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">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI)</td><td class="td" title="\n \t\t\t\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: 23% PASI‐90 semana 12<a class="elsevierStyleCrossRefs" href="#bib0915">25,26</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 manutenção: 50 mg uma vez por semana/SC \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‐2i \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psoríase em placas moderada a grave (> 10% PASI, ASC ou DLQI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% PASI‐75 semana 16<a class="elsevierStyleCrossRefs" href="#bib0915">25,30–32</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563621.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para psoríase" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Tabela 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; VO, via oral; IV, intravenosa; EASI, Eczema Area and Severity Index; ASC, área de superfície corporal; IGA, avaliação global do investigador; SCORAD, SCORing Atopic Dermatitis, PP‐NRS, Peak Pruritus Numerical Rating Scale; DA, dermatite atópica." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15‐30 mg uma vez ao dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% EASI‐75 semana 16 (30 mg)<a class="elsevierStyleCrossRef" href="#bib1005">43</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100‐200 mg uma vez ao dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% EASI‐75 semana 16 (200 mg)<a class="elsevierStyleCrossRef" href="#bib1040">50</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐4/13</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 indução: 600 mg dose única/SC \t\t\t\t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária 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% EASI‐75 semana 16<a class="elsevierStyleCrossRef" href="#bib1045">51</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 manutenção: 300 mg a cada duas semanas/SC \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‐IL‐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 indução: 500 mg semanas 0 e 2/SC \t\t\t\t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária 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">58,8% EASI‐75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1065">55</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 250 mg a cada duas semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% EASI‐75 na semana 16<a class="elsevierStyleCrossRef" href="#bib1090">60</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐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 indução: 600 mg dose única/SC \t\t\t\t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária 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% EASI‐75 semana 16<a class="elsevierStyleCrossRef" href="#bib1030">48</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 manutenção: 300 mg a cada duas semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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, 150 mg nas semanas 4, 8 e 12/IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% EASI‐75 na semana 4<a class="elsevierStyleCrossRef" href="#bib1115">65</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐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 indução: 600 mg dose única/SC \t\t\t\t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária 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 declínio de 14 pontos na semana 12<a class="elsevierStyleCrossRef" href="#bib1105">63</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 300 mg a cada duas semanas durante 10 semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no EASI na semana 12 (30 mg)<a class="elsevierStyleCrossRef" href="#bib1110">64</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐TSLP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 três meses/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (ASC ≥ 10%, IGA ≥ 3, EASI ≥ 16, SCORAD ≥ 50, PP‐NRS ≥ 4) refratária a outros tratamentos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% EASI‐50 semana 12<a class="elsevierStyleCrossRef" href="#bib1100">62</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Tópicos \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \t\t\t\t\t\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"> \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% uso tópico, uma vez/dia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 2‐3, ASC 2‐20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1125">67</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,5% tópico duas vezes/dia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 2‐3, ASC 2%‐20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no EASI na semana 4<a class="elsevierStyleCrossRef" href="#bib1120">66</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563626.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para dermatite atópica" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Tabela 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; IV, intravenosa; HiSCR, Hidradenitis Suppurativa Clinical Response; HSSI, Hidradenitis Suppurativa Severity Index." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 160 mg dia 0, 80 mg dia 15/SC \t\t\t\t\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 (estágio de Hurley II‐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">42%‐59% melhora na HiSCR em 50% dos pacientes na semana 12<a class="elsevierStyleCrossRef" href="#bib1205">83</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 manutenção: 40 mg por semana/SC ou 80 mg a cada duas semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/SC por 12 semanas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (estágio de Hurley II‐III) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1220">86</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/SC por 12 semanas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (estágio de Hurley II‐III) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% dos pacientes mostrou melhora na HiSCR na semana 12<a class="elsevierStyleCrossRef" href="#bib1225">87</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 5 mg/kg semanas 0, 2 e 6/IV \t\t\t\t\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 (estágio de Hurley II‐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">25%‐50% de melhora no HSSI na semana 8<a class="elsevierStyleCrossRef" href="#bib1210">84</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 5 mg/kg a cada oito semanas/IV \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563624.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para hidradenite supurativa" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Tabela 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; VO, via oral." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 5 mg/kg semanas 0, 2 e 6/IV \t\t\t\t\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">Doença recalcitrante e estágio tardio com doença 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% de resposta completa, 19% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1245">91</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 5 mg/kg a cada oito semanas/IV \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐TNF‐α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25‐50 mg cada semana/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doença recalcitrante e estágio tardio com doença moderada a grave (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa, 30% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260">94</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 80 mg semana 0/SC \t\t\t\t\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">Doença recalcitrante e estágio tardio com doença moderada a grave (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">77% de resposta completa, 14% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1260">94</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 40 mg a cada semana/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doença recalcitrante e estágio tardio com doença moderada a grave (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa, 21% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1240">90</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐1β \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">150‐300 mg a cada 4‐8 semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doença recalcitrante e estágio tardio com doença moderada a grave (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa, 9% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1265">95</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐12/23</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 indução: 90 mg semana 0/SC \t\t\t\t\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">Doença recalcitrante e estágio tardio com doença moderada a grave (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">71% de resposta completa, 8% de resposta parcial<a class="elsevierStyleCrossRef" href="#bib1270">96</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 45 mg semanas 4 e 8/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Doença recalcitrante e estágio tardio com doença moderada a grave (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2/2 resposta completa após um a 15 meses<a class="elsevierStyleCrossRef" href="#bib1240">90</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563625.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para pioderma gangrenoso" ] ] 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" => "SC, subcutânea; IV, intravenosa; UAS7, Urticaria Activity Score por 7 dias seguidos." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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‐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">150‐300 mg a cada quatro semanas/SC \t\t\t\t\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 sintomáticos apesar da dose de anti‐H1 4×</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75,3% de resposta completa em 40 semanas<a class="elsevierStyleCrossRef" href="#bib1290">100</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 refratária, considerar 600 mg a cada quatro semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IgE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72‐240 mg a cada quatro semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 sintomáticos apesar da dose de anti‐H1 4× \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa na semana 12<a class="elsevierStyleCrossRefs" href="#bib1300">102,103</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 indução: 150 mg nas semanas 0, 1, 2 e 3/SC Manutenção: 150 mg a cada duas semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária ao omalizumabe (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Redução de 82% no UAS7 na semana 12<a class="elsevierStyleCrossRef" href="#bib1330">108</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐4/13</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 indução: 600 mg semana 0/SC \t\t\t\t\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">Refratária ao omalizumabe (no contexto da 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">Melhora em uma série de casos de seis pacientes<a class="elsevierStyleCrossRef" href="#bib1315">105</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 300 mg a cada duas semanas/SC \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‐SIGLEC‐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: 0,3 mg/kg no dia 0 \t\t\t\t\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 sintomáticos apesar da dose de anti‐H1 4× (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">92% de resposta completa em 22 semanas<a class="elsevierStyleCrossRef" href="#bib1310">104</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">Não</td><td class="td" title="\n \t\t\t\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: 1 mg/kg nos dias 29, 57, 85, 113 e 141/IV \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‐IL‐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 indução: 30 mg a cada quatro semanas por três doses/SC \t\t\t\t\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 refratária 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% de resposta completa em 20 semanas<a class="elsevierStyleCrossRef" href="#bib1320">106</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 30 mg a cada oito semanas/SC \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IL‐5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100‐300 mg a cada quatro semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratária ao antiH1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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">106</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563620.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para urticária espontânea crônica" ] ] 7 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Tabela 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "VO, via oral." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de perda de cabelos no couro cabeludo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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%‐38% de restauração capilar adequada na semana 36<a class="elsevierStyleCrossRef" href="#bib1335">109</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de perda de cabelos no couro cabeludo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa e 58% de restauração capilar adequada durante quatro a 18 meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1345">111</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de perda de cabelos no couro cabeludo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% dos pacientes apresentam >80% de restauração capilar em seis meses<a class="elsevierStyleCrossRef" href="#bib1350">112</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de perda de cabelos no couro cabeludo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa e 64% de restauração capilar adequada durante seis meses de tratamento<a class="elsevierStyleCrossRef" href="#bib1340">110</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563622.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para alopecia areata" ] ] 8 => array:8 [ "identificador" => "tbl0035" "etiqueta" => "Tabela 7" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at7" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; IV, intravenosa; PDAI, Pemphigus Disease and Area Index." "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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐CD20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 ocasiões com intervalo de duas semanas/IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratários a esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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, 89% de resposta completa em 24 meses<a class="elsevierStyleCrossRef" href="#bib1360">114</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (FcRn) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10‐25 mg semanalmente durante quatro semanas/IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratários a esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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, resposta completa em 64% dos pacientes em 2‐41 semanas<a class="elsevierStyleCrossRef" href="#bib1380">118</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐BLyS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/kg IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratários a esteroides (no contexto de pesquisa) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diminuição de 73% no escore médio de PDAI na semana 12<a class="elsevierStyleCrossRef" href="#bib1390">120</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐CD20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/m2 a cada 1‐4 semanas até 500 mg semanalmente por duas semanas/IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratário a esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70,5% de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395">121</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IgE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100‐525 mg a cada uma a quatro semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 refratário a esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% de resposta completa em seis meses<a class="elsevierStyleCrossRef" href="#bib1395">121</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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‐IL‐4/13</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 indução: dose única de 600 mg/SC \t\t\t\t\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 refratário 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">66,7% de resposta completa em 4,5 meses<a class="elsevierStyleCrossRef" href="#bib1395">121</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 300 mg a cada duas semanas/SC \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563623.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para doenças bolhosas" ] ] 9 => array:8 [ "identificador" => "tbl0040" "etiqueta" => "Tabela 8" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at8" "detalle" => "Tabela " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "SC, subcutânea; VO, via oral; RC, resposta completa." "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">Doença \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 \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 ação \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 administração \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">Indicação \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">Eficácia \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 \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">Nível de evidência \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 recomendação \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/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‐TNF‐α</td><td class="td" title="\n \t\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 kg: 25 mg dias 0 e 3/SC \t\t\t\t\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 7,6%<a class="elsevierStyleCrossRef" href="#bib1420">126</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">Não</td><td class="td" title="\n \t\t\t\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">>65 kg: 50 mg dias 0 e 3/SC \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐TNF‐α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/kg dose única/IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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%<a class="elsevierStyleCrossRef" href="#bib1425">127</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Líquen 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‐TNF‐α</td><td class="td" title="\n \t\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 indução: 80 mg semana 0/SC, 40 mg semana 1/SC \t\t\t\t\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">2ª linha em LP mucoso, 3ª linha em LP cutâneo</td><td class="td" title="\n \t\t\t\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 cicatrização de lesões cutâneas durante um período de seis meses<a class="elsevierStyleCrossRef" href="#bib1455">133</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">Não</td><td class="td" title="\n \t\t\t\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 manutenção: 40 mg a cada duas semanas SC \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,5% tópico duas vezes ao dia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Líquen plano cutâneo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diminuição de 7,6 pontos de mCAILS em quatro semanas<a class="elsevierStyleCrossRef" href="#bib1460">134</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Líquen plano pilar e líquen plano hipertrófico \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no LPPAI em 12 semanas no líquen plano pilar<a class="elsevierStyleCrossRef" href="#bib1515">145</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Lúpus Eritematoso Cutâneo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐IFN‐γ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/IV a cada quatro semanas \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 cutâneos no contexto de lúpus eritematoso sistêmico \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% dos pacientes alcançaram redução no escore CLASI ≥ 50%<a class="elsevierStyleCrossRef" href="#bib1490">140</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1,5% tópico duas vezes ao dia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% ASC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no VASI em 30% dos pacientes na semana 24<a class="elsevierStyleCrossRef" href="#bib1495">141</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% tópico duas vezes/dia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% ASC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% no VASI em quatro meses (áreas expostas ao sol)<a class="elsevierStyleCrossRef" href="#bib1500">142</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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% ASC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diminuição de 5,4% na ASC em 50% dos pacientes<a class="elsevierStyleCrossRef" href="#bib1505">143</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratário à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (apenas relatos de casos)<a class="elsevierStyleCrossRef" href="#bib1520">146</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 séries de casos<a class="elsevierStyleCrossRef" href="#bib1520">146</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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/DRESS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (apenas relatos de casos)<a class="elsevierStyleCrossRefs" href="#bib1445">131,132</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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‐TNF‐α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 única /SC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (apenas relatos de casos)<a class="elsevierStyleCrossRefs" href="#bib1445">131,132</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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">Síndrome hipereosinofílica \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (apenas relatos de casos)<a class="elsevierStyleCrossRef" href="#bib1525">147</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 manhã‐10 mg à noite/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 (apenas relatos de casos)<a class="elsevierStyleCrossRef" href="#bib1475">137</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 1/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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/dia/VO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Refratária à esteroides \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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">149</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Não \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3563627.png" ] ] ] ] "descripcion" => array:1 [ "pt" => "Terapias imunológicas direcionadas para outras doenças" ] ] 10 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 16297 ] ] ] "bibliografia" => array:2 [ "titulo" => "Referências" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:158 [ 0 => array:3 [ "identificador" => "bib0795" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monoclonal antibody therapeutics: history and future" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.coph.2012.08.001" "Revista" => array:6 [ …6] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0800" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Different approaches for obtaining antibodies from human B cells" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0805" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dermatology" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:5 [ …5] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0810" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Signaling pathways in inflammation and anti‐inflammatory therapies" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2174/1381612824666180327165604" "Revista" => array:6 [ …6] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0815" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Yamauchi PS, editor. Biologic and systemic agents in dermatology. 1st ed. 2018. Cham: Springer International Publishing: Imprint: Springer; 2018. p.1." ] ] ] 5 => array:3 [ "identificador" => "bib0820" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200107263450403" "Revista" => array:6 [ …6] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0825" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.290.23.3073" "Revista" => array:6 [ …6] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0830" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 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Estatísticas

Artigo Original

Terapia direcionada para doenças imunomediadas da pele. O que o dermatologista deve saber?

Edinson López, Raúl Cabrera

Autor para correspondência

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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3104

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que se leu este artigo

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          "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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    "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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    "fechaRecibido" => "2023-08-25"
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            0 => "Agentes de imunomodula&#231;&#227;o"
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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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        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Fluxograma PRISMA&#46;</p>"
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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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                  \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" scope="col" style="border-bottom: 2px solid black">Mecanismo de a&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \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" scope="col" style="border-bottom: 2px solid black">Indica&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efic&#225;cia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FDA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \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
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                  \t\t\t\t\ttable-head\n
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                  \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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">IL&#8208;23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \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
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                  \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
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                  \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>"
        ]
      ]
      3 => array:8 [
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        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
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            "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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        "etiqueta" => "Tabela 4"
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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>"
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            0 => array:2 [
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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">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>
                  """
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          "pt" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para pioderma gangrenoso</p>"
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      6 => array:8 [
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        "etiqueta" => "Tabela 5"
        "tipo" => "MULTIMEDIATABLA"
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            "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 [
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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">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>"
        ]
      ]
      7 => array:8 [
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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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          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Terapias imunol&#243;gicas direcionadas para alopecia areata</p>"
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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>"
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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
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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>"
          "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">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>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3563627.png"
              ]
            ]
          ]
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Informação do artigo

ISSN: 26662752
Idioma original: Português

DOI:10.1016/j.abdp.2024.03.009

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