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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de sobrevida mostrando o efeito conjunto dos dois principais preditores de interrup&#231;&#227;o da medica&#231;&#227;o&#58; a interleucina &#40;IL&#41;&#8208;6 e o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#41;&#46; Pode&#8208;se observar que os pacientes com n&#237;veis mais elevados de DLQI e IL&#8208;6 tiveram quase 75&#37; de chance de mudan&#231;a do tratamento sist&#234;mico no per&#237;odo de seguimento&#46; <span class="elsevierStyleItalic">mIL6</span>&#44; escores medianos de IL&#8208;6<span class="elsevierStyleHsp" style=""></span>da popula&#231;&#227;o atual &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo do valor mediano&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima do valor mediano&#41;&#46; <span class="elsevierStyleItalic">mDLQI</span>&#44; escore DLQI da popula&#231;&#227;o atual&#59; 0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo de 5&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima ou igual a 5&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a cr&#244;nica que afeta entre 1&#37; e 3&#37; da popula&#231;&#227;o global&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#44;2</span></a> A revolu&#231;&#227;o no desenvolvimento de novos medicamentos biol&#243;gicos e pequenas mol&#233;culas &#233; apoiada por ensaios cl&#237;nicos de alta qualidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;4</span></a> Esses medicamentos agem por meio do bloqueio modulado de citocinas envolvidas na patog&#234;nese da psor&#237;ase&#44; reduzindo a ocorr&#234;ncia de eventos adversos e alcan&#231;ando resultados melhores em compara&#231;&#227;o aos imunossupressores cl&#225;ssicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">5&#44;6</span></a> Como novos medicamentos est&#227;o constantemente sendo lan&#231;ados no mercado&#44; a necessidade de dados direcionados &#224; farmacovigil&#226;ncia de imunossupressores para o tratamento da psor&#237;ase est&#225; sendo constantemente enfatizada&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;8</span></a> O n&#250;mero de registros ativos para monitoramento de eventos adversos ainda &#233; insuficiente&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a que afeta a pele e outros &#243;rg&#227;os por meio de inflama&#231;&#227;o sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">11&#8208;13</span></a> A doen&#231;a tamb&#233;m tem impacto significante na qualidade de vida do paciente&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> Em geral&#44; os dados de farmacovigil&#226;ncia s&#227;o escassos nos pa&#237;ses em desenvolvimento&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a> O Sistema &#218;nico de Sa&#250;de &#40;SUS&#41; brasileiro &#233; respons&#225;vel pela presta&#231;&#227;o de cuidados de sa&#250;de e assist&#234;ncia farmac&#234;utica a mais de 200 milh&#245;es de pessoas&#59;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a> portanto&#44; o SUS brasileiro constitui cen&#225;rio privilegiado para a farmacovigil&#226;ncia&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> O protocolo nacional referente &#224; sequ&#234;ncia de medicamentos utilizados na psor&#237;ase n&#227;o &#233; diferente da maioria das recomenda&#231;&#245;es internacionais&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O objetivo do presente estudo foi avaliar a sobrevida de medicamentos na psor&#237;ase moderada a grave&#44; al&#233;m de avaliar se as citocinas s&#233;ricas podem ser utilizadas para prever a falha terap&#234;utica na psor&#237;ase e a ocorr&#234;ncia de infec&#231;&#227;o grave&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">De janeiro de 2016 a dezembro de 2017&#44; foram inclu&#237;dos consecutivamente pacientes atendidos no Ambulat&#243;rio de Psor&#237;ase do Hospital Universit&#225;rio de Bras&#237;lia&#44; Universidade de Bras&#237;lia&#44; Brasil&#46; Esse principal hospital de refer&#234;ncia atende uma &#225;rea urbana com mais de tr&#234;s milh&#245;es de habitantes em Bras&#237;lia&#46; Essa estrat&#233;gia garantiu a valida&#231;&#227;o interna das frequ&#234;ncias&#46; Avalia&#231;&#245;es adicionais&#44; incluindo preditores e efeitos de risco&#44; foram implementadas de acordo com estrat&#233;gia <span class="elsevierStyleItalic">post&#8208;hoc</span>&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Crit&#233;rio de inclus&#227;o</span><p id="par0025" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos pacientes com diagn&#243;stico de psor&#237;ase moderada a grave estabelecido por meio de avalia&#231;&#227;o cl&#237;nica por dois dermatologistas certificados&#46; Sempre que necess&#225;rio&#44; foram realizadas bi&#243;psias de pele&#46; Foram exclu&#237;dos pacientes com diagn&#243;stico concomitante de artrite psori&#225;sica ou outras doen&#231;as autoimunes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Avalia&#231;&#227;o basal</span><p id="par0030" class="elsevierStylePara elsevierViewall">Todos os pacientes foram submetidos a avalia&#231;&#227;o inicial composta por formul&#225;rio padronizado para informa&#231;&#245;es demogr&#225;ficas&#44; informa&#231;&#245;es sobre o tratamento atual e sobre tratamentos anteriores&#46; De acordo com a literatura atual e a classifica&#231;&#227;o internacional de doen&#231;as&#44; os pacientes que apresentavam o padr&#227;o mais comum de psor&#237;ase em placas&#44; associado ou n&#227;o a les&#245;es palmoplantares&#44; ungueais ou no couro cabeludo&#44; foram classificados como portadores de psor&#237;ase em placa&#46; Os pacientes classificados como psor&#237;ase do couro cabeludo&#44; psor&#237;ase ungueal&#44; psor&#237;ase pustulosa palmoplantar&#44; psor&#237;ase gutata e psor&#237;ase invertida apresentavam les&#245;es exclusivamente nessas localiza&#231;&#245;es&#46; Os medicamentos utilizados no momento da inclus&#227;o foram considerados como os medicamentos basais&#46; O &#205;ndice de &#193;rea e Gravidade da Psor&#237;ase &#40;PASI&#44; Psoriasis Area and Severity Index&#41;&#44; a &#225;rea de superf&#237;cie corporal &#40;ASC&#41;&#44; o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#44; Dermatology Life Quality Index&#41; e o &#205;ndice de Gravidade da Psor&#237;ase Ungueal &#40;NAPSI&#44; Nail Psoriasis Severity Index&#41; foram avaliados sempre que poss&#237;vel&#46; Dados retrospectivos sobre medicamentos e hist&#243;rico de doen&#231;as antes da inclus&#227;o apresentaram perdas importantes&#44; e essas informa&#231;&#245;es foram retiradas da avalia&#231;&#227;o dos resultados&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">O sangue total foi coletado por venopun&#231;&#227;o cubital&#46; O soro de cada paciente foi isolado&#44; e Interleucina&#8208;2 &#40;IL&#8208;2&#41;&#44; IL&#8208;4&#44; IL&#8208;6&#44; IL&#8208;10&#44; IL&#8208;17A&#44; interferon &#40;IFN&#41;&#8208;&#947; e fator de necrose tumoral &#40;TNF&#41;&#8208;&#945; foram medidos usando o BD&#8482; Cytometric Bead Array &#40;CBA&#41; Human Th1&#47;Th2&#47;Th17 Cytokine Kit &#40;Becton Dickinson&#44; Franklin Lakes&#44; EUA&#41; com cit&#244;metro de fluxo FACSVerse &#40;Becton Dickinson&#41;&#46; Todas as an&#225;lises foram feitas em triplicata&#44; e os valores foram normalizados e comparados com os obtidos de 47 controles saud&#225;veis &#40;m&#233;dia de idade<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42 anos e 3 meses&#44; 18 homens e 29 mulheres recrutados na mesma institui&#231;&#227;o&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Consultas de seguimento</span><p id="par0040" class="elsevierStylePara elsevierViewall">Os pacientes foram acompanhados at&#233; dezembro de 2021 &#40;at&#233; seis anos&#41; por dermatologista por meio de consulta cl&#237;nica a cada tr&#234;s a seis meses&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Desfecho prim&#225;rio</span><p id="par0045" class="elsevierStylePara elsevierViewall">A sobrevida do medicamento foi medida de acordo com o tempo de interrup&#231;&#227;o da medica&#231;&#227;o basal &#40;mudan&#231;a ou suspens&#227;o&#41;&#46; O desfecho prim&#225;rio foi considerado a ocorr&#234;ncia de interrup&#231;&#227;o do medicamento&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Desfechos secund&#225;rios</span><p id="par0050" class="elsevierStylePara elsevierViewall">Como desfechos secund&#225;rios&#44; foram consideradas as ocorr&#234;ncias de falha terap&#234;utica ou infec&#231;&#227;o grave&#46; A falha terap&#234;utica foi definida como a necessidade de modifica&#231;&#227;o do tratamento em decorr&#234;ncia do mau controle da doen&#231;a &#40;escores PASI&#44; ASC&#44; DLQI e NAPSI acima de 10&#41;&#46; Infec&#231;&#227;o grave foi definida como qualquer infec&#231;&#227;o que levasse &#224; suspens&#227;o do tratamento cl&#237;nico por mais de um m&#234;s&#46; A incid&#234;ncia de desfechos adicionais&#44; como rea&#231;&#245;es adversas&#44; tamb&#233;m foi avaliada&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Preditores</span><p id="par0055" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas basais cl&#237;nicas e laboratoriais relevantes que foram avaliadas como candidatos a preditores de sobrevida do medicamento inclu&#237;ram sexo&#44; idade&#44; tabagismo e abuso de &#225;lcool&#44; bem como citocinas pr&#243;&#8208;inflamat&#243;rias &#40;IL&#8208;2&#44; IL&#8208;6&#44; IL&#8208;17A&#44; IFN&#8208;&#947; TNF&#8208;&#945;&#41; e anti&#8208;inflamat&#243;rias &#40;IL&#8208;4&#44; IL&#8208;10&#41;&#46; Na linha basal&#44; os pacientes que estavam em uso apenas de biol&#243;gicos e que nunca haviam utilizado outros medicamentos biol&#243;gicos foram classificados como &#8220;<span class="elsevierStyleItalic">na&#239;ve</span>&#8221;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lise estat&#237;stica</span><p id="par0060" class="elsevierStylePara elsevierViewall">Os preditores foram avaliados utilizando testes de log&#8208;rank&#46; A censura de dados foi definida para ocorrer quando os pacientes fossem perdidos no seguimento&#46; As vari&#225;veis num&#233;ricas n&#227;o foram categorizadas na an&#225;lise univariada&#46; Para a an&#225;lise ajustada&#44; os n&#237;veis de citocinas foram categorizados de acordo com o valor mediano da popula&#231;&#227;o global ou como positivo&#47;negativo se mais de 30&#37; dos pacientes apresentassem resultados negativos&#46; As demais vari&#225;veis num&#233;ricas foram categorizadas apenas para gera&#231;&#227;o de gr&#225;ficos&#46; Os valores de PASI e ASC foram calculados apenas para pacientes com psor&#237;ase em placas&#46; Os dados ausentes n&#227;o foram substitu&#237;dos&#44; e os pacientes com dados ausentes foram exclu&#237;dos de an&#225;lises espec&#237;ficas&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Para o desfecho prim&#225;rio&#44; foi utilizado modelo multivariado ajustado&#46; Preditores que atingiram baixo limiar de evid&#234;ncia &#40;p &#8804; 0&#44;100&#41; com base na an&#225;lise univariada foram inclu&#237;dos&#46; Foram calculadas as taxas de risco &#40;HRs&#44; do ingl&#234;s <span class="elsevierStyleItalic">hazard ratios</span>&#41; utilizando modelo de risco proporcional de Cox&#46; Todas as suposi&#231;&#245;es foram cuidadosamente avaliadas&#46; Foram utilizados os pacotes <span class="elsevierStyleItalic">survival</span> e <span class="elsevierStyleItalic">survminer</span> do R Studio &#40;R Studio&#44; Viena&#44; &#193;ustria&#41;&#46; Para desfechos secund&#225;rios&#44; foi utilizada uma estrat&#233;gia de an&#225;lise de subgrupo&#46; A compara&#231;&#227;o gr&#225;fica dos n&#237;veis de citocinas foi realizada usando GraphPad Prism vers&#227;o 8&#46;0&#46;0 para Windows &#40;GraphPad Software&#44; San Diego&#44; EUA&#41;&#46; A signific&#226;ncia estat&#237;stica foi definida por valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 e um intervalo de confian&#231;a de 95&#37; &#40;IC95&#37;&#41; apropriado&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">&#201;tica</span><p id="par0070" class="elsevierStylePara elsevierViewall">O presente estudo foi aprovado pelo Comit&#234; de &#201;tica da Faculdade de Medicina da Universidade de Bras&#237;lia&#46; Todos os pacientes foram inclu&#237;dos ap&#243;s a assinatura do termo de consentimento informado&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0075" class="elsevierStylePara elsevierViewall">Foram acompanhados 262 pacientes com psor&#237;ase&#59; 133 &#40;50&#44;76&#37;&#41; do sexo masculino e 129 &#40;49&#44;24&#37;&#41; do sexo feminino&#46; A maioria dos pacientes apresentava psor&#237;ase em placas &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>222&#59; 84&#44;73&#37;&#41;&#46; Tamb&#233;m foram inclu&#237;dos pacientes com psor&#237;ase do couro cabeludo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#59; 4&#44;58&#37;&#41;&#44; ungueal &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#59; 1&#44;91&#37;&#41;&#44; pustulosa palmoplantar &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; 3&#44;05&#37;&#41;&#44; gutata &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#59; 4&#44;96&#37;&#41; e psor&#237;ase invertida &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#59; 0&#44;76&#37;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">No presente estudo&#44; 71 &#40;27&#44;10&#37;&#41; pacientes n&#227;o faziam uso de imunossupressores sist&#234;micos &#91;nove &#40;3&#44;44&#37;&#41; estavam sem nenhum tratamento&#44; cinco &#40;1&#44;91&#37;&#41; faziam fototerapia isolada&#44; 50 &#40;19&#44;08&#37;&#41; faziam uso de corticoide t&#243;pico e sete &#40;2&#44;67&#37;&#41; faziam uso de acitretina&#93;&#59; 96 &#40;36&#44;64&#37;&#41; pacientes utilizavam imunossupressores cl&#225;ssicos &#91;94 &#40;35&#44;88&#37;&#41; utilizavam metotrexato e dois &#40;0&#44;76&#37;&#41; corticoides sist&#234;micos&#93;&#59; 75 pacientes &#40;28&#44;63&#37;&#41; faziam uso de biol&#243;gicos anti&#8208;TNF &#91;22 &#40;8&#44;39&#37;&#41; usavam adalimumabe&#44; 29 &#40;11&#44;07&#37;&#41; usavam etanercepte e 24 &#40;9&#44;16&#37;&#41; usavam infliximabe&#93;&#59; e 20 pacientes &#40;7&#44;63&#37;&#41; faziam uso de medicamentos anti&#8208;IL &#91;nove &#40;3&#44;44&#37;&#41; utilizavam ustequinumabe e 11 &#40;4&#44;19&#37;&#41; secuquinumabe&#93;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O tempo m&#233;dio de seguimento foi de 4&#44;88 anos &#40;intervalo<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#8208;6 anos&#41;&#46; Interrup&#231;&#227;o da medica&#231;&#227;o antes do final do tempo de seguimento do estudo foi identificada em 122 &#40;46&#44;56&#37;&#41; pacientes&#59; 88 &#40;33&#44;58&#37;&#41; pacientes tiveram falha terap&#234;utica isolada identificada&#44; e 18 &#40;6&#44;87&#37;&#41; tiveram infec&#231;&#227;o grave isolada que levou &#224; suspens&#227;o do tratamento&#46; Dezesseis pacientes &#40;6&#44;11&#37;&#41; interromperam o tratamento por infec&#231;&#227;o grave simult&#226;nea e falha terap&#234;utica&#46; No total&#44; 34 &#40;12&#44;97&#37;&#41; pacientes apresentaram infec&#231;&#245;es graves &#40;25 tiveram infec&#231;&#245;es de vias a&#233;reas superiores n&#227;o identificadas&#44; oito pacientes tiveram diagn&#243;stico de COVID&#8208;19 e um paciente teve infec&#231;&#227;o gastrintestinal grave&#41;&#46; Al&#233;m disso&#44; os dados de apenas cinco pacientes foram censurados &#40;considerados perda de seguimento&#41; em decorr&#234;ncia de outros eventos adversos relatados&#46; Esses eventos foram avaliados apenas de maneira descritiva em virtude do baixo n&#250;mero de eventos&#46; Um paciente desenvolveu hidradenite supurativa durante o tratamento com acitretina&#44; dois pacientes apresentaram sinais de neuropatia durante o uso de metotrexato&#44; um paciente apresentou dispneia durante o uso de metotrexato e um paciente apresentou sinais de insufici&#234;ncia renal inicial durante o uso de infliximabe&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Perfil de citocinas</span><p id="par0090" class="elsevierStylePara elsevierViewall">O uso de imunossupressores cl&#225;ssicos&#44; principalmente o metotrexato&#44; foi associado a importante supress&#227;o de citocinas pr&#243;&#8208;inflamat&#243;rias &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Para alguns mediadores&#44; como IL&#8208;17 e TNF&#8208;&#945;&#44; o efeito supressor do metotrexato foi ainda maior do que o observado em pacientes em uso de biol&#243;gicos anti&#8208;TNF ou anti&#8208;IL&#46; Os n&#237;veis basais de IL&#8208;6 aumentaram significantemente em pacientes com taxas de sobrevida da medica&#231;&#227;o mais baixas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">An&#225;lise de sobrevida de medicamento</span><p id="par0095" class="elsevierStylePara elsevierViewall">A an&#225;lise univariada &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41; mostrou que os valores basais de PASI &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41;&#44; DLQI &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e NAPSI &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; foram significantemente maiores nos pacientes que interromperam o tratamento sist&#234;mico&#46; A IL&#8208;6 foi o &#250;nico marcador inflamat&#243;rio significantemente elevado nos pacientes que interromperam a medica&#231;&#227;o basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">No presente modelo multivariado&#44; foi observado que cada eleva&#231;&#227;o de um ponto no escore de DLQI elevou a chance de mudan&#231;a de tratamento em 1&#44;04 vezes com IC95&#37; muito estreitos &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;04&#59; IC95&#37; 1&#44;01&#8211;1&#44;07&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; Al&#233;m disso&#44; pacientes que apresentavam n&#237;veis basais de IL&#8208;6 iguais ou acima do valor mediano da popula&#231;&#227;o total tiveram chance quase duas vezes maior de interromper o tratamento sist&#234;mico do que pacientes com n&#237;veis mais baixos do marcador pr&#243;&#8208;inflamat&#243;rio &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;99&#59; IC95&#37; 1&#44;29&#8211;3&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#59; <a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; Informa&#231;&#245;es detalhadas relacionadas &#224; an&#225;lise de subgrupos podem ser encontradas no Arquivo <a class="elsevierStyleCrossRef" href="#sec0095">Suplementar 1 &#40;tabelas A e B&#41;</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0105" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a inflamat&#243;ria complexa&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">19</span></a> &#201; did&#225;tico considerar que o in&#237;cio da cascata inflamat&#243;ria &#233; causado conjuntamente por est&#237;mulos de fatores ambientais associados &#224; suscetibilidade gen&#233;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">20&#44;21</span></a> Esses est&#237;mulos ativam c&#233;lulas apresentadoras de ant&#237;genos&#44; macr&#243;fagos e c&#233;lulas dendr&#237;ticas para produzir citocinas coordenadoras &#40;TNF&#44; IL&#8208;23&#44; IFN&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">20</span></a> Subsequentemente&#44; a ativa&#231;&#227;o das vias Th1 e Th17 resulta na ativa&#231;&#227;o de citocinas finais&#44; como IL&#8208;17&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">22</span></a> Por fim&#44; queratin&#243;citos inflamados tamb&#233;m expressam mediadores inflamat&#243;rios&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">A utilidade de medir citocinas no sangue de pacientes com doen&#231;as da pele est&#225; em debate&#46; Embora a maioria dos estudos destaque os efeitos aut&#243;crinos e par&#225;crinos desses mediadores na psor&#237;ase&#44; praticamente todas as citocinas envolvidas t&#234;m efeito semelhante ao end&#243;crino&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">23&#44;24</span></a> Cataldi et al&#46; descobriram que os mediadores plasm&#225;ticos da via Th17 eram significantemente maiores em uma popula&#231;&#227;o de 70 pacientes com psor&#237;ase do que em um grupo de controle&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">No presente estudo&#44; a eleva&#231;&#227;o de IL&#8208;6 foi o marcador pr&#243;&#8208;inflamat&#243;rio mais consistente para interrup&#231;&#227;o do tratamento&#46; Embora a IL&#8208;6 seja um mediador pr&#243;&#8208;inflamat&#243;rio&#44; o uso de tocilizumabe&#44; um biol&#243;gico humanizado recombinante anti&#8208;IL&#8208;6&#44; levou a resultados imprevis&#237;veis na psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">26&#44;27</span></a> Estudos que avaliaram o ambiente inflamat&#243;rio da pele n&#227;o inclu&#237;ram a express&#227;o da IL&#8208;6 na principal via patog&#234;nica da psor&#237;ase&#46; Nakajima et al&#46;&#44; em 2010&#44; descobriram que a IL&#8208;6 n&#227;o era crucial para o desenvolvimento de dermatite semelhante &#224; psor&#237;ase independente de c&#233;lulas T em um modelo murino&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> O mesmo resultado foi encontrado para IL&#8208;17&#44; um dos principais alvos modernos para o tratamento da psor&#237;ase&#44; mostrando que o perfil inflamat&#243;rio humano pode ser imprevis&#237;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Curiosamente&#44; em concord&#226;ncia com os achados do presente estudo&#44; dados anteriores que avaliaram popula&#231;&#245;es menores refor&#231;am o papel da IL&#8208;6 circulante na previs&#227;o da resposta ao tratamento na psor&#237;ase&#46; Zalewska et al&#46; descobriram que os n&#237;veis plasm&#225;ticos de IL&#8208;6 eram consistentemente elevados em 106 pacientes com psor&#237;ase n&#227;o tratados e que n&#237;veis elevados desses mediadores estavam relacionados a uma resposta insatisfat&#243;ria ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; v&#225;rios estudos relacionaram os n&#237;veis de IL&#8208;6 circulante ao perfil de inflama&#231;&#227;o sist&#234;mica de pacientes com psor&#237;ase&#44; incluindo a ocorr&#234;ncia de artrite psori&#225;sica e dislipidemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">30&#8208;37</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">&#201; poss&#237;vel que a IL&#8208;6 n&#227;o seja muito importante para desencadear a cascata inflamat&#243;ria da psor&#237;ase no ambiente cut&#226;neo&#44; mas seu efeito supressor nas c&#233;lulas T reguladoras pode explicar por que esse mediador &#233; um marcador muito importante para a resposta ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> Al&#233;m disso&#44; estudos anteriores mostraram que a IL&#8208;6 &#233; um dos mediadores inflamat&#243;rios com os efeitos sist&#234;micos mais importantes&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">23</span></a> A modula&#231;&#227;o conjunta de IL&#8208;6 e outras citocinas&#44; como a obtida por inibidores de Janus quinase&#44; pode ser estrat&#233;gia interessante para casos refrat&#225;rios&#44; como demonstrado por ensaios cl&#237;nicos de fase dois&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Os medicamentos cl&#225;ssicos&#44; principalmente o metotrexato&#44; foram associados a n&#237;veis mais baixos de TNF e IL&#8208;17 &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46; Considerando que o metotrexato &#233; clinicamente menos eficaz do que os biol&#243;gicos&#44; levantou&#8208;se a hip&#243;tese de que uma supress&#227;o intensa dos dois principais mediadores da psor&#237;ase n&#227;o est&#225; diretamente correlacionada com as respostas ao tratamento&#46; Por outro lado&#44; pacientes que respondem ao metotrexato podem apresentar quadros mais leves de psor&#237;ase e&#44; consequentemente&#44; n&#237;veis mais baixos de TNF e IL&#8208;17&#46; Infelizmente&#44; no presente estudo n&#227;o foram medidas as citocinas inflamat&#243;rias em diferentes momentos&#46; A avalia&#231;&#227;o seriada de longo prazo desses marcadores pode oferecer melhores pistas para &#224; patog&#234;nese da psor&#237;ase&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; no presente estudo&#44; escores ruins de marcadores cl&#237;nicos tradicionais&#44; incluindo PASI&#44; DLQI e NAPSI&#44; foram significantemente relacionados &#224; redu&#231;&#227;o da sobrevida do medicamento&#46; Esse resultado era esperado&#44; uma vez que esses par&#226;metros s&#227;o preditores internacionalmente reconhecidos de troca de medicamentos&#46; O &#237;ndice de qualidade de vida &#40;DLQI&#41; teve a maior influ&#234;ncia na sobrevida medicamentosa entre os escores cl&#237;nicos avaliados&#46; A principal limita&#231;&#227;o de qualquer estudo de coorte &#233; a presen&#231;a de fatores de confus&#227;o que n&#227;o podem ser tratados por randomiza&#231;&#227;o&#46; Entretanto&#44; os resultados de IL&#8208;6 foram consistentes na an&#225;lise laboratorial&#44; na an&#225;lise univariada e no modelo multivariado&#46; Esse resultado tamb&#233;m representa uma reprodu&#231;&#227;o de estudos anteriores em popula&#231;&#245;es menores&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a> Al&#233;m disso&#44; o objetivo do presente estudo foi apenas medir os n&#237;veis basais de citocinas como marcadores de longo prazo para a gravidade da psor&#237;ase&#46; M&#250;ltiplas medidas em diferentes momentos podem ajudar a elucidar o papel dos marcadores s&#233;ricos na evolu&#231;&#227;o da psor&#237;ase e seu tratamento&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclus&#227;o</span><p id="par0140" class="elsevierStylePara elsevierViewall">O presente estudo mostrou que a qualidade de vida reduzida e os n&#237;veis s&#233;ricos elevados de IL&#8208;6 foram preditores da baixa sobrevida de medicamento em pacientes com psor&#237;ase moderada a grave&#46; Tamb&#233;m pode&#8208;se concluir que&#44; embora a IL&#8208;6 n&#227;o seja o mediador mais importante da via inflamat&#243;ria no ambiente cut&#226;neo&#44; &#233; um biomarcador candidato interessante para predizer a resposta sist&#234;mica ao tratamento da psor&#237;ase&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Suporte financeiro</span><p id="par0145" class="elsevierStylePara elsevierViewall">A pesquisa recebeu suporte financeiro da Funda&#231;&#227;o de Apoio &#224; Pesquisa do Distrito Federal &#40;FAP&#8208;DF&#41;&#59; N&#250;meros de concess&#227;o&#58; FINATEC 7044 e 7155&#59; e da Funda&#231;&#227;o La Roche Posay&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Contribui&#231;&#227;o dos autores</span><p id="par0150" class="elsevierStylePara elsevierViewall">Nat&#225;lia Ribeiro de Magalh&#227;es Alves&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Patr&#237;cia Shu Kurizky&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; administra&#231;&#227;o do projeto&#44; supervis&#227;o&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Licia Maria Henrique da Mota&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Cleandro Pires de Albuquerque&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Juliana Tomaz Esper&#58; Investiga&#231;&#227;o&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Aridne Souza Costa Campos&#58; Investiga&#231;&#227;o&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Vit&#243;ria Pereira Reis&#58; Investiga&#231;&#227;o&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Henrique Metzker Ferro&#58; Investiga&#231;&#227;o&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Natalia Gil&#8208;Jaramillo&#58; Investiga&#231;&#227;o&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Joaquim Pedro Brito&#8208;de&#8208;Sousa&#58; Investiga&#231;&#227;o&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Luana Cabral Le&#227;o Leal&#58; Investiga&#231;&#227;o&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Ot&#225;vio de Toledo N&#243;brega&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Carla Nunes de Ara&#250;jo&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; supervis&#227;o&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Agenor de Castro Moreira dos Santos J&#250;nior&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Gladys Aires Martins&#58; Investiga&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Olindo Assis Martins Filho&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Ciro Martins Gomes&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; administra&#231;&#227;o do projeto&#44; obten&#231;&#227;o de financiamento&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflito de interesses</span><p id="par0235" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dados prim&#225;rios do mundo real sobre o tratamento da psor&#237;ase s&#227;o escassos&#44; especialmente no que diz respeito ao papel dos biomarcadores sol&#250;veis como preditores de resultados&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Foi avaliada a utilidade das citocinas s&#233;ricas Th1&#47;Th17 juntamente com as caracter&#237;sticas cl&#237;nicas como preditores de sobrevida de medicamentos no tratamento da psor&#237;ase&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos consecutivamente participantes com psor&#237;ase moderada a grave que foram acompanhados por seis anos&#46; N&#237;veis basais de interferon&#8208;&#945;&#44; fator de necrose tumoral&#8208;&#945; e interleucina &#40;IL&#41;&#8208;2&#44; IL&#8208;4&#44; IL&#8208;6&#44; IL&#8208;10 e IL&#8208;17A foram medidos utilizando matriz de esferas citom&#233;tricas&#59; dados cl&#237;nicos foram avaliados&#46; Foram calculadas as taxas de risco &#40;HR&#44; do ingl&#234;s <span class="elsevierStyleItalic">hazard ratios</span>&#41; para a sobrevida de medicamentos usando modelo de risco proporcional de Cox&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 262 pacientes&#44; a maioria em uso de imunossupressores sist&#234;micos ou biol&#243;gicos&#46; No modelo multivariado&#44; qualidade de vida ruim medida pelo <span class="elsevierStyleItalic">Dermatology Life Quality Index</span> &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;04&#59; IC95&#37; 1&#44;01&#8211;1&#44;07&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41; e IL&#8208;6 basal elevada &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;99&#59; IC95&#37; 1&#44;29&#8211;3&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; estavam associados &#224; interrup&#231;&#227;o do tratamento&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A principal limita&#231;&#227;o de qualquer estudo de coorte &#233; a presen&#231;a de fatores de confus&#227;o que n&#227;o puderam ser detectados na avalia&#231;&#227;o cl&#237;nica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A m&#225; qualidade de vida e o n&#237;vel s&#233;rico basal elevado de IL&#8208;6 previram a interrup&#231;&#227;o do tratamento em pacientes com psor&#237;ase moderada a grave&#46; Embora a IL&#8208;6 n&#227;o seja o mediador mais importante da via inflamat&#243;ria no ambiente cut&#226;neo&#44; &#233; um biomarcador candidato interessante para prever a resposta ao tratamento da psor&#237;ase&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Como citar este artigo&#58; Alves NR&#44; Kurizky PS&#44; da Mota LM&#44; de Albuquerque CP&#44; Esper JT&#44; Campos AS&#44; et al&#46; Elevated serum IL&#8208;6 levels predict treatment interruption in patients with moderate to severe psoriasis&#58; a 6&#8208;year real&#8208;world cohort study&#46; An Bras Dermatol&#46; 2024&#59;99&#58;34&#8211;42&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Trabalho realizado no Servi&#231;o de Dermatologia&#44; Hospital Universit&#225;rio de Bras&#237;lia&#44; Bras&#237;lia&#44; DF&#44; Brasil&#59; Instituto Ren&#233; Rachou&#44; Funda&#231;&#227;o Oswaldo Cruz&#44; Fiocruz Minas&#44; Belo Horizonte&#44; MG&#44; Brasil&#46;</p>"
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        "etiqueta" => "Figura 1"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de citocinas em pacientes com psor&#237;ase de acordo com o tipo de terapia imunossupressora basal no momento da inclus&#227;o&#46; Os dados s&#227;o mostrados como distribui&#231;&#227;o de dispers&#227;o de valores individuais em gr&#225;ficos de barras representando n&#237;veis de medianas de cada citocina&#46; <span class="elsevierStyleItalic">IL</span>&#44; interleucina&#59; <span class="elsevierStyleItalic">TNF</span>&#44; fator de necrose tumoral&#59; <span class="elsevierStyleItalic">IFN</span>&#44; interferon&#59; <span class="elsevierStyleItalic">CS</span>&#44; controles saud&#225;veis&#59; <span class="elsevierStyleItalic">Sem</span>&#44; pacientes com psor&#237;ase sem uso de imunossupressores sist&#234;micos&#59; <span class="elsevierStyleItalic">Cl&#225;ssico</span>&#44; pacientes com psor&#237;ase em uso de imunossupressores cl&#225;ssicos&#59; <span class="elsevierStyleItalic">&#945;&#8208;TNF</span>&#44; pacientes com psor&#237;ase em uso de agentes antifator de necrose tumoral&#59; <span class="elsevierStyleItalic">&#945;&#8208;IL</span>&#44; pacientes com psor&#237;ase em uso de agentes anti&#8208;IL&#46; Os valores de p para todos os grupos que apresentaram diferen&#231;a significante s&#227;o mostrados na parte inferior de cada gr&#225;fico&#46; Valores de p n&#227;o significantes &#40;&#62; 0&#44;05&#41; n&#227;o s&#227;o representados&#46;</p>"
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de citocinas em pacientes com psor&#237;ase de acordo com a sobrevida do medicamento estratificada por 1 a 4 anos e 5 a 6 anos&#46; Os dados s&#227;o mostrados como distribui&#231;&#227;o de dispers&#227;o de valores individuais em gr&#225;ficos de barras representando n&#237;veis m&#233;dios de cada citocina&#46; IL&#44; interleucina&#59; TNF&#44; fator de necrose tumoral&#59; IFN&#44; interferon&#59; CS&#44; controles saud&#225;veis&#46; Os valores de p para todos os grupos que apresentaram diferen&#231;a significante s&#227;o mostrados na parte inferior de cada gr&#225;fico&#46; Valores de p n&#227;o significantes &#40;&#62; 0&#44;05&#41; n&#227;o s&#227;o representados&#46;</p>"
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de sobrevida mostrando o efeito conjunto dos dois principais preditores de interrup&#231;&#227;o da medica&#231;&#227;o&#58; a interleucina &#40;IL&#41;&#8208;6 e o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#41;&#46; Pode&#8208;se observar que os pacientes com n&#237;veis mais elevados de DLQI e IL&#8208;6 tiveram quase 75&#37; de chance de mudan&#231;a do tratamento sist&#234;mico no per&#237;odo de seguimento&#46; <span class="elsevierStyleItalic">mIL6</span>&#44; escores medianos de IL&#8208;6<span class="elsevierStyleHsp" style=""></span>da popula&#231;&#227;o atual &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo do valor mediano&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima do valor mediano&#41;&#46; <span class="elsevierStyleItalic">mDLQI</span>&#44; escore DLQI da popula&#231;&#227;o atual&#59; 0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo de 5&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima ou igual a 5&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Idade&#58; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">H&#225;bito de tabagismo&#44; n&#160;&#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Abuso de &#225;lcool&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;2&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;890<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></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
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;4&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;6&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;10&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;17A&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IFN&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Falhas terap&#234;uticas anteriores&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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Artigo original
Níveis séricos elevados de IL‐6 predizem a interrupção do tratamento em pacientes com psoríase moderada a grave: estudo de coorte de seis anos no mundo real
Natália Ribeiro de Magalhães Alvesa, Patrícia Shu Kurizkya,b, Licia Maria Henrique da Motaa,c,d, Cleandro Pires de Albuquerquea,c, Juliana Tomaz Espera,b, Aridne Souza Costa Camposa,b, Vitoria Pereira Reisa, Henrique Metzker Ferroa, Natalia Gil‐Jaramilloe, Joaquim Pedro Brito‐de‐Sousaf, Luana Cabral Leão Leala, Otávio de Toledo Nóbregaa, Carla Nunes de Araújoa,e, Agenor de Castro Moreira dos Santos Júniora,g, Gladys Aires Martinsb, Olindo Assis Martins Filhoh, Ciro Martins Gomesa,d,g,
Corresponding author
cirogomes@unb.br

Autor para correspondência.
a Programa de Pós‐Graduação de Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brasil
b Serviço de Dermatologia, Hospital Universitário de Brasília, Brasília, DF, Brasil
c Serviço de Reumatologia, Hospital Universitário de Brasília, Brasília, DF, Brasil
d Programa de Pós‐Graduação em Patologia Molecular, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brasil
e Laboratório de Interação Patógeno‐Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, DF, Brasil
f Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brasil
g Laboratório Central de Saúde Pública do Distrito Federal, Secretaria de Saúde do Distrito Federal, Brasília, DF, Brasil
h Instituto René Rachou, Fundação Oswaldo Cruz, Fiocruz Minas, Belo Horizonte, MG, Brasil
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de sobrevida mostrando o efeito conjunto dos dois principais preditores de interrup&#231;&#227;o da medica&#231;&#227;o&#58; a interleucina &#40;IL&#41;&#8208;6 e o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#41;&#46; Pode&#8208;se observar que os pacientes com n&#237;veis mais elevados de DLQI e IL&#8208;6 tiveram quase 75&#37; de chance de mudan&#231;a do tratamento sist&#234;mico no per&#237;odo de seguimento&#46; <span class="elsevierStyleItalic">mIL6</span>&#44; escores medianos de IL&#8208;6<span class="elsevierStyleHsp" style=""></span>da popula&#231;&#227;o atual &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo do valor mediano&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima do valor mediano&#41;&#46; <span class="elsevierStyleItalic">mDLQI</span>&#44; escore DLQI da popula&#231;&#227;o atual&#59; 0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo de 5&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima ou igual a 5&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a cr&#244;nica que afeta entre 1&#37; e 3&#37; da popula&#231;&#227;o global&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#44;2</span></a> A revolu&#231;&#227;o no desenvolvimento de novos medicamentos biol&#243;gicos e pequenas mol&#233;culas &#233; apoiada por ensaios cl&#237;nicos de alta qualidade&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">3&#44;4</span></a> Esses medicamentos agem por meio do bloqueio modulado de citocinas envolvidas na patog&#234;nese da psor&#237;ase&#44; reduzindo a ocorr&#234;ncia de eventos adversos e alcan&#231;ando resultados melhores em compara&#231;&#227;o aos imunossupressores cl&#225;ssicos&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">5&#44;6</span></a> Como novos medicamentos est&#227;o constantemente sendo lan&#231;ados no mercado&#44; a necessidade de dados direcionados &#224; farmacovigil&#226;ncia de imunossupressores para o tratamento da psor&#237;ase est&#225; sendo constantemente enfatizada&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;8</span></a> O n&#250;mero de registros ativos para monitoramento de eventos adversos ainda &#233; insuficiente&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a que afeta a pele e outros &#243;rg&#227;os por meio de inflama&#231;&#227;o sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">11&#8208;13</span></a> A doen&#231;a tamb&#233;m tem impacto significante na qualidade de vida do paciente&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> Em geral&#44; os dados de farmacovigil&#226;ncia s&#227;o escassos nos pa&#237;ses em desenvolvimento&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">15</span></a> O Sistema &#218;nico de Sa&#250;de &#40;SUS&#41; brasileiro &#233; respons&#225;vel pela presta&#231;&#227;o de cuidados de sa&#250;de e assist&#234;ncia farmac&#234;utica a mais de 200 milh&#245;es de pessoas&#59;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">16</span></a> portanto&#44; o SUS brasileiro constitui cen&#225;rio privilegiado para a farmacovigil&#226;ncia&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> O protocolo nacional referente &#224; sequ&#234;ncia de medicamentos utilizados na psor&#237;ase n&#227;o &#233; diferente da maioria das recomenda&#231;&#245;es internacionais&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">O objetivo do presente estudo foi avaliar a sobrevida de medicamentos na psor&#237;ase moderada a grave&#44; al&#233;m de avaliar se as citocinas s&#233;ricas podem ser utilizadas para prever a falha terap&#234;utica na psor&#237;ase e a ocorr&#234;ncia de infec&#231;&#227;o grave&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">De janeiro de 2016 a dezembro de 2017&#44; foram inclu&#237;dos consecutivamente pacientes atendidos no Ambulat&#243;rio de Psor&#237;ase do Hospital Universit&#225;rio de Bras&#237;lia&#44; Universidade de Bras&#237;lia&#44; Brasil&#46; Esse principal hospital de refer&#234;ncia atende uma &#225;rea urbana com mais de tr&#234;s milh&#245;es de habitantes em Bras&#237;lia&#46; Essa estrat&#233;gia garantiu a valida&#231;&#227;o interna das frequ&#234;ncias&#46; Avalia&#231;&#245;es adicionais&#44; incluindo preditores e efeitos de risco&#44; foram implementadas de acordo com estrat&#233;gia <span class="elsevierStyleItalic">post&#8208;hoc</span>&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Crit&#233;rio de inclus&#227;o</span><p id="par0025" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos pacientes com diagn&#243;stico de psor&#237;ase moderada a grave estabelecido por meio de avalia&#231;&#227;o cl&#237;nica por dois dermatologistas certificados&#46; Sempre que necess&#225;rio&#44; foram realizadas bi&#243;psias de pele&#46; Foram exclu&#237;dos pacientes com diagn&#243;stico concomitante de artrite psori&#225;sica ou outras doen&#231;as autoimunes&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Avalia&#231;&#227;o basal</span><p id="par0030" class="elsevierStylePara elsevierViewall">Todos os pacientes foram submetidos a avalia&#231;&#227;o inicial composta por formul&#225;rio padronizado para informa&#231;&#245;es demogr&#225;ficas&#44; informa&#231;&#245;es sobre o tratamento atual e sobre tratamentos anteriores&#46; De acordo com a literatura atual e a classifica&#231;&#227;o internacional de doen&#231;as&#44; os pacientes que apresentavam o padr&#227;o mais comum de psor&#237;ase em placas&#44; associado ou n&#227;o a les&#245;es palmoplantares&#44; ungueais ou no couro cabeludo&#44; foram classificados como portadores de psor&#237;ase em placa&#46; Os pacientes classificados como psor&#237;ase do couro cabeludo&#44; psor&#237;ase ungueal&#44; psor&#237;ase pustulosa palmoplantar&#44; psor&#237;ase gutata e psor&#237;ase invertida apresentavam les&#245;es exclusivamente nessas localiza&#231;&#245;es&#46; Os medicamentos utilizados no momento da inclus&#227;o foram considerados como os medicamentos basais&#46; O &#205;ndice de &#193;rea e Gravidade da Psor&#237;ase &#40;PASI&#44; Psoriasis Area and Severity Index&#41;&#44; a &#225;rea de superf&#237;cie corporal &#40;ASC&#41;&#44; o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#44; Dermatology Life Quality Index&#41; e o &#205;ndice de Gravidade da Psor&#237;ase Ungueal &#40;NAPSI&#44; Nail Psoriasis Severity Index&#41; foram avaliados sempre que poss&#237;vel&#46; Dados retrospectivos sobre medicamentos e hist&#243;rico de doen&#231;as antes da inclus&#227;o apresentaram perdas importantes&#44; e essas informa&#231;&#245;es foram retiradas da avalia&#231;&#227;o dos resultados&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">O sangue total foi coletado por venopun&#231;&#227;o cubital&#46; O soro de cada paciente foi isolado&#44; e Interleucina&#8208;2 &#40;IL&#8208;2&#41;&#44; IL&#8208;4&#44; IL&#8208;6&#44; IL&#8208;10&#44; IL&#8208;17A&#44; interferon &#40;IFN&#41;&#8208;&#947; e fator de necrose tumoral &#40;TNF&#41;&#8208;&#945; foram medidos usando o BD&#8482; Cytometric Bead Array &#40;CBA&#41; Human Th1&#47;Th2&#47;Th17 Cytokine Kit &#40;Becton Dickinson&#44; Franklin Lakes&#44; EUA&#41; com cit&#244;metro de fluxo FACSVerse &#40;Becton Dickinson&#41;&#46; Todas as an&#225;lises foram feitas em triplicata&#44; e os valores foram normalizados e comparados com os obtidos de 47 controles saud&#225;veis &#40;m&#233;dia de idade<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42 anos e 3 meses&#44; 18 homens e 29 mulheres recrutados na mesma institui&#231;&#227;o&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Consultas de seguimento</span><p id="par0040" class="elsevierStylePara elsevierViewall">Os pacientes foram acompanhados at&#233; dezembro de 2021 &#40;at&#233; seis anos&#41; por dermatologista por meio de consulta cl&#237;nica a cada tr&#234;s a seis meses&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Desfecho prim&#225;rio</span><p id="par0045" class="elsevierStylePara elsevierViewall">A sobrevida do medicamento foi medida de acordo com o tempo de interrup&#231;&#227;o da medica&#231;&#227;o basal &#40;mudan&#231;a ou suspens&#227;o&#41;&#46; O desfecho prim&#225;rio foi considerado a ocorr&#234;ncia de interrup&#231;&#227;o do medicamento&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Desfechos secund&#225;rios</span><p id="par0050" class="elsevierStylePara elsevierViewall">Como desfechos secund&#225;rios&#44; foram consideradas as ocorr&#234;ncias de falha terap&#234;utica ou infec&#231;&#227;o grave&#46; A falha terap&#234;utica foi definida como a necessidade de modifica&#231;&#227;o do tratamento em decorr&#234;ncia do mau controle da doen&#231;a &#40;escores PASI&#44; ASC&#44; DLQI e NAPSI acima de 10&#41;&#46; Infec&#231;&#227;o grave foi definida como qualquer infec&#231;&#227;o que levasse &#224; suspens&#227;o do tratamento cl&#237;nico por mais de um m&#234;s&#46; A incid&#234;ncia de desfechos adicionais&#44; como rea&#231;&#245;es adversas&#44; tamb&#233;m foi avaliada&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Preditores</span><p id="par0055" class="elsevierStylePara elsevierViewall">As caracter&#237;sticas basais cl&#237;nicas e laboratoriais relevantes que foram avaliadas como candidatos a preditores de sobrevida do medicamento inclu&#237;ram sexo&#44; idade&#44; tabagismo e abuso de &#225;lcool&#44; bem como citocinas pr&#243;&#8208;inflamat&#243;rias &#40;IL&#8208;2&#44; IL&#8208;6&#44; IL&#8208;17A&#44; IFN&#8208;&#947; TNF&#8208;&#945;&#41; e anti&#8208;inflamat&#243;rias &#40;IL&#8208;4&#44; IL&#8208;10&#41;&#46; Na linha basal&#44; os pacientes que estavam em uso apenas de biol&#243;gicos e que nunca haviam utilizado outros medicamentos biol&#243;gicos foram classificados como &#8220;<span class="elsevierStyleItalic">na&#239;ve</span>&#8221;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">An&#225;lise estat&#237;stica</span><p id="par0060" class="elsevierStylePara elsevierViewall">Os preditores foram avaliados utilizando testes de log&#8208;rank&#46; A censura de dados foi definida para ocorrer quando os pacientes fossem perdidos no seguimento&#46; As vari&#225;veis num&#233;ricas n&#227;o foram categorizadas na an&#225;lise univariada&#46; Para a an&#225;lise ajustada&#44; os n&#237;veis de citocinas foram categorizados de acordo com o valor mediano da popula&#231;&#227;o global ou como positivo&#47;negativo se mais de 30&#37; dos pacientes apresentassem resultados negativos&#46; As demais vari&#225;veis num&#233;ricas foram categorizadas apenas para gera&#231;&#227;o de gr&#225;ficos&#46; Os valores de PASI e ASC foram calculados apenas para pacientes com psor&#237;ase em placas&#46; Os dados ausentes n&#227;o foram substitu&#237;dos&#44; e os pacientes com dados ausentes foram exclu&#237;dos de an&#225;lises espec&#237;ficas&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Para o desfecho prim&#225;rio&#44; foi utilizado modelo multivariado ajustado&#46; Preditores que atingiram baixo limiar de evid&#234;ncia &#40;p &#8804; 0&#44;100&#41; com base na an&#225;lise univariada foram inclu&#237;dos&#46; Foram calculadas as taxas de risco &#40;HRs&#44; do ingl&#234;s <span class="elsevierStyleItalic">hazard ratios</span>&#41; utilizando modelo de risco proporcional de Cox&#46; Todas as suposi&#231;&#245;es foram cuidadosamente avaliadas&#46; Foram utilizados os pacotes <span class="elsevierStyleItalic">survival</span> e <span class="elsevierStyleItalic">survminer</span> do R Studio &#40;R Studio&#44; Viena&#44; &#193;ustria&#41;&#46; Para desfechos secund&#225;rios&#44; foi utilizada uma estrat&#233;gia de an&#225;lise de subgrupo&#46; A compara&#231;&#227;o gr&#225;fica dos n&#237;veis de citocinas foi realizada usando GraphPad Prism vers&#227;o 8&#46;0&#46;0 para Windows &#40;GraphPad Software&#44; San Diego&#44; EUA&#41;&#46; A signific&#226;ncia estat&#237;stica foi definida por valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 e um intervalo de confian&#231;a de 95&#37; &#40;IC95&#37;&#41; apropriado&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">&#201;tica</span><p id="par0070" class="elsevierStylePara elsevierViewall">O presente estudo foi aprovado pelo Comit&#234; de &#201;tica da Faculdade de Medicina da Universidade de Bras&#237;lia&#46; Todos os pacientes foram inclu&#237;dos ap&#243;s a assinatura do termo de consentimento informado&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0075" class="elsevierStylePara elsevierViewall">Foram acompanhados 262 pacientes com psor&#237;ase&#59; 133 &#40;50&#44;76&#37;&#41; do sexo masculino e 129 &#40;49&#44;24&#37;&#41; do sexo feminino&#46; A maioria dos pacientes apresentava psor&#237;ase em placas &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>222&#59; 84&#44;73&#37;&#41;&#46; Tamb&#233;m foram inclu&#237;dos pacientes com psor&#237;ase do couro cabeludo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#59; 4&#44;58&#37;&#41;&#44; ungueal &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#59; 1&#44;91&#37;&#41;&#44; pustulosa palmoplantar &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; 3&#44;05&#37;&#41;&#44; gutata &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#59; 4&#44;96&#37;&#41; e psor&#237;ase invertida &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#59; 0&#44;76&#37;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">No presente estudo&#44; 71 &#40;27&#44;10&#37;&#41; pacientes n&#227;o faziam uso de imunossupressores sist&#234;micos &#91;nove &#40;3&#44;44&#37;&#41; estavam sem nenhum tratamento&#44; cinco &#40;1&#44;91&#37;&#41; faziam fototerapia isolada&#44; 50 &#40;19&#44;08&#37;&#41; faziam uso de corticoide t&#243;pico e sete &#40;2&#44;67&#37;&#41; faziam uso de acitretina&#93;&#59; 96 &#40;36&#44;64&#37;&#41; pacientes utilizavam imunossupressores cl&#225;ssicos &#91;94 &#40;35&#44;88&#37;&#41; utilizavam metotrexato e dois &#40;0&#44;76&#37;&#41; corticoides sist&#234;micos&#93;&#59; 75 pacientes &#40;28&#44;63&#37;&#41; faziam uso de biol&#243;gicos anti&#8208;TNF &#91;22 &#40;8&#44;39&#37;&#41; usavam adalimumabe&#44; 29 &#40;11&#44;07&#37;&#41; usavam etanercepte e 24 &#40;9&#44;16&#37;&#41; usavam infliximabe&#93;&#59; e 20 pacientes &#40;7&#44;63&#37;&#41; faziam uso de medicamentos anti&#8208;IL &#91;nove &#40;3&#44;44&#37;&#41; utilizavam ustequinumabe e 11 &#40;4&#44;19&#37;&#41; secuquinumabe&#93;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O tempo m&#233;dio de seguimento foi de 4&#44;88 anos &#40;intervalo<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#8208;6 anos&#41;&#46; Interrup&#231;&#227;o da medica&#231;&#227;o antes do final do tempo de seguimento do estudo foi identificada em 122 &#40;46&#44;56&#37;&#41; pacientes&#59; 88 &#40;33&#44;58&#37;&#41; pacientes tiveram falha terap&#234;utica isolada identificada&#44; e 18 &#40;6&#44;87&#37;&#41; tiveram infec&#231;&#227;o grave isolada que levou &#224; suspens&#227;o do tratamento&#46; Dezesseis pacientes &#40;6&#44;11&#37;&#41; interromperam o tratamento por infec&#231;&#227;o grave simult&#226;nea e falha terap&#234;utica&#46; No total&#44; 34 &#40;12&#44;97&#37;&#41; pacientes apresentaram infec&#231;&#245;es graves &#40;25 tiveram infec&#231;&#245;es de vias a&#233;reas superiores n&#227;o identificadas&#44; oito pacientes tiveram diagn&#243;stico de COVID&#8208;19 e um paciente teve infec&#231;&#227;o gastrintestinal grave&#41;&#46; Al&#233;m disso&#44; os dados de apenas cinco pacientes foram censurados &#40;considerados perda de seguimento&#41; em decorr&#234;ncia de outros eventos adversos relatados&#46; Esses eventos foram avaliados apenas de maneira descritiva em virtude do baixo n&#250;mero de eventos&#46; Um paciente desenvolveu hidradenite supurativa durante o tratamento com acitretina&#44; dois pacientes apresentaram sinais de neuropatia durante o uso de metotrexato&#44; um paciente apresentou dispneia durante o uso de metotrexato e um paciente apresentou sinais de insufici&#234;ncia renal inicial durante o uso de infliximabe&#46;</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Perfil de citocinas</span><p id="par0090" class="elsevierStylePara elsevierViewall">O uso de imunossupressores cl&#225;ssicos&#44; principalmente o metotrexato&#44; foi associado a importante supress&#227;o de citocinas pr&#243;&#8208;inflamat&#243;rias &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Para alguns mediadores&#44; como IL&#8208;17 e TNF&#8208;&#945;&#44; o efeito supressor do metotrexato foi ainda maior do que o observado em pacientes em uso de biol&#243;gicos anti&#8208;TNF ou anti&#8208;IL&#46; Os n&#237;veis basais de IL&#8208;6 aumentaram significantemente em pacientes com taxas de sobrevida da medica&#231;&#227;o mais baixas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">An&#225;lise de sobrevida de medicamento</span><p id="par0095" class="elsevierStylePara elsevierViewall">A an&#225;lise univariada &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41; mostrou que os valores basais de PASI &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41;&#44; DLQI &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e NAPSI &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; foram significantemente maiores nos pacientes que interromperam o tratamento sist&#234;mico&#46; A IL&#8208;6 foi o &#250;nico marcador inflamat&#243;rio significantemente elevado nos pacientes que interromperam a medica&#231;&#227;o basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">No presente modelo multivariado&#44; foi observado que cada eleva&#231;&#227;o de um ponto no escore de DLQI elevou a chance de mudan&#231;a de tratamento em 1&#44;04 vezes com IC95&#37; muito estreitos &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;04&#59; IC95&#37; 1&#44;01&#8211;1&#44;07&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41;&#46; Al&#233;m disso&#44; pacientes que apresentavam n&#237;veis basais de IL&#8208;6 iguais ou acima do valor mediano da popula&#231;&#227;o total tiveram chance quase duas vezes maior de interromper o tratamento sist&#234;mico do que pacientes com n&#237;veis mais baixos do marcador pr&#243;&#8208;inflamat&#243;rio &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;99&#59; IC95&#37; 1&#44;29&#8211;3&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#59; <a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46; Informa&#231;&#245;es detalhadas relacionadas &#224; an&#225;lise de subgrupos podem ser encontradas no Arquivo <a class="elsevierStyleCrossRef" href="#sec0095">Suplementar 1 &#40;tabelas A e B&#41;</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0105" class="elsevierStylePara elsevierViewall">A psor&#237;ase &#233; doen&#231;a inflamat&#243;ria complexa&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">19</span></a> &#201; did&#225;tico considerar que o in&#237;cio da cascata inflamat&#243;ria &#233; causado conjuntamente por est&#237;mulos de fatores ambientais associados &#224; suscetibilidade gen&#233;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">20&#44;21</span></a> Esses est&#237;mulos ativam c&#233;lulas apresentadoras de ant&#237;genos&#44; macr&#243;fagos e c&#233;lulas dendr&#237;ticas para produzir citocinas coordenadoras &#40;TNF&#44; IL&#8208;23&#44; IFN&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">20</span></a> Subsequentemente&#44; a ativa&#231;&#227;o das vias Th1 e Th17 resulta na ativa&#231;&#227;o de citocinas finais&#44; como IL&#8208;17&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">22</span></a> Por fim&#44; queratin&#243;citos inflamados tamb&#233;m expressam mediadores inflamat&#243;rios&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">A utilidade de medir citocinas no sangue de pacientes com doen&#231;as da pele est&#225; em debate&#46; Embora a maioria dos estudos destaque os efeitos aut&#243;crinos e par&#225;crinos desses mediadores na psor&#237;ase&#44; praticamente todas as citocinas envolvidas t&#234;m efeito semelhante ao end&#243;crino&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">23&#44;24</span></a> Cataldi et al&#46; descobriram que os mediadores plasm&#225;ticos da via Th17 eram significantemente maiores em uma popula&#231;&#227;o de 70 pacientes com psor&#237;ase do que em um grupo de controle&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">25</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">No presente estudo&#44; a eleva&#231;&#227;o de IL&#8208;6 foi o marcador pr&#243;&#8208;inflamat&#243;rio mais consistente para interrup&#231;&#227;o do tratamento&#46; Embora a IL&#8208;6 seja um mediador pr&#243;&#8208;inflamat&#243;rio&#44; o uso de tocilizumabe&#44; um biol&#243;gico humanizado recombinante anti&#8208;IL&#8208;6&#44; levou a resultados imprevis&#237;veis na psor&#237;ase&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">26&#44;27</span></a> Estudos que avaliaram o ambiente inflamat&#243;rio da pele n&#227;o inclu&#237;ram a express&#227;o da IL&#8208;6 na principal via patog&#234;nica da psor&#237;ase&#46; Nakajima et al&#46;&#44; em 2010&#44; descobriram que a IL&#8208;6 n&#227;o era crucial para o desenvolvimento de dermatite semelhante &#224; psor&#237;ase independente de c&#233;lulas T em um modelo murino&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> O mesmo resultado foi encontrado para IL&#8208;17&#44; um dos principais alvos modernos para o tratamento da psor&#237;ase&#44; mostrando que o perfil inflamat&#243;rio humano pode ser imprevis&#237;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Curiosamente&#44; em concord&#226;ncia com os achados do presente estudo&#44; dados anteriores que avaliaram popula&#231;&#245;es menores refor&#231;am o papel da IL&#8208;6 circulante na previs&#227;o da resposta ao tratamento na psor&#237;ase&#46; Zalewska et al&#46; descobriram que os n&#237;veis plasm&#225;ticos de IL&#8208;6 eram consistentemente elevados em 106 pacientes com psor&#237;ase n&#227;o tratados e que n&#237;veis elevados desses mediadores estavam relacionados a uma resposta insatisfat&#243;ria ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a> Al&#233;m disso&#44; v&#225;rios estudos relacionaram os n&#237;veis de IL&#8208;6 circulante ao perfil de inflama&#231;&#227;o sist&#234;mica de pacientes com psor&#237;ase&#44; incluindo a ocorr&#234;ncia de artrite psori&#225;sica e dislipidemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">30&#8208;37</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">&#201; poss&#237;vel que a IL&#8208;6 n&#227;o seja muito importante para desencadear a cascata inflamat&#243;ria da psor&#237;ase no ambiente cut&#226;neo&#44; mas seu efeito supressor nas c&#233;lulas T reguladoras pode explicar por que esse mediador &#233; um marcador muito importante para a resposta ao tratamento&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> Al&#233;m disso&#44; estudos anteriores mostraram que a IL&#8208;6 &#233; um dos mediadores inflamat&#243;rios com os efeitos sist&#234;micos mais importantes&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">23</span></a> A modula&#231;&#227;o conjunta de IL&#8208;6 e outras citocinas&#44; como a obtida por inibidores de Janus quinase&#44; pode ser estrat&#233;gia interessante para casos refrat&#225;rios&#44; como demonstrado por ensaios cl&#237;nicos de fase dois&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">39</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Os medicamentos cl&#225;ssicos&#44; principalmente o metotrexato&#44; foram associados a n&#237;veis mais baixos de TNF e IL&#8208;17 &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46; Considerando que o metotrexato &#233; clinicamente menos eficaz do que os biol&#243;gicos&#44; levantou&#8208;se a hip&#243;tese de que uma supress&#227;o intensa dos dois principais mediadores da psor&#237;ase n&#227;o est&#225; diretamente correlacionada com as respostas ao tratamento&#46; Por outro lado&#44; pacientes que respondem ao metotrexato podem apresentar quadros mais leves de psor&#237;ase e&#44; consequentemente&#44; n&#237;veis mais baixos de TNF e IL&#8208;17&#46; Infelizmente&#44; no presente estudo n&#227;o foram medidas as citocinas inflamat&#243;rias em diferentes momentos&#46; A avalia&#231;&#227;o seriada de longo prazo desses marcadores pode oferecer melhores pistas para &#224; patog&#234;nese da psor&#237;ase&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; no presente estudo&#44; escores ruins de marcadores cl&#237;nicos tradicionais&#44; incluindo PASI&#44; DLQI e NAPSI&#44; foram significantemente relacionados &#224; redu&#231;&#227;o da sobrevida do medicamento&#46; Esse resultado era esperado&#44; uma vez que esses par&#226;metros s&#227;o preditores internacionalmente reconhecidos de troca de medicamentos&#46; O &#237;ndice de qualidade de vida &#40;DLQI&#41; teve a maior influ&#234;ncia na sobrevida medicamentosa entre os escores cl&#237;nicos avaliados&#46; A principal limita&#231;&#227;o de qualquer estudo de coorte &#233; a presen&#231;a de fatores de confus&#227;o que n&#227;o podem ser tratados por randomiza&#231;&#227;o&#46; Entretanto&#44; os resultados de IL&#8208;6 foram consistentes na an&#225;lise laboratorial&#44; na an&#225;lise univariada e no modelo multivariado&#46; Esse resultado tamb&#233;m representa uma reprodu&#231;&#227;o de estudos anteriores em popula&#231;&#245;es menores&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a> Al&#233;m disso&#44; o objetivo do presente estudo foi apenas medir os n&#237;veis basais de citocinas como marcadores de longo prazo para a gravidade da psor&#237;ase&#46; M&#250;ltiplas medidas em diferentes momentos podem ajudar a elucidar o papel dos marcadores s&#233;ricos na evolu&#231;&#227;o da psor&#237;ase e seu tratamento&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclus&#227;o</span><p id="par0140" class="elsevierStylePara elsevierViewall">O presente estudo mostrou que a qualidade de vida reduzida e os n&#237;veis s&#233;ricos elevados de IL&#8208;6 foram preditores da baixa sobrevida de medicamento em pacientes com psor&#237;ase moderada a grave&#46; Tamb&#233;m pode&#8208;se concluir que&#44; embora a IL&#8208;6 n&#227;o seja o mediador mais importante da via inflamat&#243;ria no ambiente cut&#226;neo&#44; &#233; um biomarcador candidato interessante para predizer a resposta sist&#234;mica ao tratamento da psor&#237;ase&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Suporte financeiro</span><p id="par0145" class="elsevierStylePara elsevierViewall">A pesquisa recebeu suporte financeiro da Funda&#231;&#227;o de Apoio &#224; Pesquisa do Distrito Federal &#40;FAP&#8208;DF&#41;&#59; N&#250;meros de concess&#227;o&#58; FINATEC 7044 e 7155&#59; e da Funda&#231;&#227;o La Roche Posay&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Contribui&#231;&#227;o dos autores</span><p id="par0150" class="elsevierStylePara elsevierViewall">Nat&#225;lia Ribeiro de Magalh&#227;es Alves&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Patr&#237;cia Shu Kurizky&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; administra&#231;&#227;o do projeto&#44; supervis&#227;o&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Licia Maria Henrique da Mota&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Cleandro Pires de Albuquerque&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Juliana Tomaz Esper&#58; Investiga&#231;&#227;o&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Aridne Souza Costa Campos&#58; Investiga&#231;&#227;o&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Vit&#243;ria Pereira Reis&#58; Investiga&#231;&#227;o&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Henrique Metzker Ferro&#58; Investiga&#231;&#227;o&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Natalia Gil&#8208;Jaramillo&#58; Investiga&#231;&#227;o&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Joaquim Pedro Brito&#8208;de&#8208;Sousa&#58; Investiga&#231;&#227;o&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Luana Cabral Le&#227;o Leal&#58; Investiga&#231;&#227;o&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Ot&#225;vio de Toledo N&#243;brega&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Carla Nunes de Ara&#250;jo&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; supervis&#227;o&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Agenor de Castro Moreira dos Santos J&#250;nior&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Gladys Aires Martins&#58; Investiga&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Olindo Assis Martins Filho&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; rascunho original&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; supervis&#227;o&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Ciro Martins Gomes&#58; Investiga&#231;&#227;o&#44; reda&#231;&#227;o &#8211; revis&#227;o e edi&#231;&#227;o&#44; administra&#231;&#227;o do projeto&#44; obten&#231;&#227;o de financiamento&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflito de interesses</span><p id="par0235" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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            1 => "Biomarcadores"
            2 => "Doen&#231;as autoimunes"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Dados prim&#225;rios do mundo real sobre o tratamento da psor&#237;ase s&#227;o escassos&#44; especialmente no que diz respeito ao papel dos biomarcadores sol&#250;veis como preditores de resultados&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivo</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Foi avaliada a utilidade das citocinas s&#233;ricas Th1&#47;Th17 juntamente com as caracter&#237;sticas cl&#237;nicas como preditores de sobrevida de medicamentos no tratamento da psor&#237;ase&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos consecutivamente participantes com psor&#237;ase moderada a grave que foram acompanhados por seis anos&#46; N&#237;veis basais de interferon&#8208;&#945;&#44; fator de necrose tumoral&#8208;&#945; e interleucina &#40;IL&#41;&#8208;2&#44; IL&#8208;4&#44; IL&#8208;6&#44; IL&#8208;10 e IL&#8208;17A foram medidos utilizando matriz de esferas citom&#233;tricas&#59; dados cl&#237;nicos foram avaliados&#46; Foram calculadas as taxas de risco &#40;HR&#44; do ingl&#234;s <span class="elsevierStyleItalic">hazard ratios</span>&#41; para a sobrevida de medicamentos usando modelo de risco proporcional de Cox&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 262 pacientes&#44; a maioria em uso de imunossupressores sist&#234;micos ou biol&#243;gicos&#46; No modelo multivariado&#44; qualidade de vida ruim medida pelo <span class="elsevierStyleItalic">Dermatology Life Quality Index</span> &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;04&#59; IC95&#37; 1&#44;01&#8211;1&#44;07&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#41; e IL&#8208;6 basal elevada &#40;HR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;99&#59; IC95&#37; 1&#44;29&#8211;3&#44;08&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; estavam associados &#224; interrup&#231;&#227;o do tratamento&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A principal limita&#231;&#227;o de qualquer estudo de coorte &#233; a presen&#231;a de fatores de confus&#227;o que n&#227;o puderam ser detectados na avalia&#231;&#227;o cl&#237;nica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A m&#225; qualidade de vida e o n&#237;vel s&#233;rico basal elevado de IL&#8208;6 previram a interrup&#231;&#227;o do tratamento em pacientes com psor&#237;ase moderada a grave&#46; Embora a IL&#8208;6 n&#227;o seja o mediador mais importante da via inflamat&#243;ria no ambiente cut&#226;neo&#44; &#233; um biomarcador candidato interessante para prever a resposta ao tratamento da psor&#237;ase&#46;</p></span>"
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          "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de citocinas em pacientes com psor&#237;ase de acordo com o tipo de terapia imunossupressora basal no momento da inclus&#227;o&#46; Os dados s&#227;o mostrados como distribui&#231;&#227;o de dispers&#227;o de valores individuais em gr&#225;ficos de barras representando n&#237;veis de medianas de cada citocina&#46; <span class="elsevierStyleItalic">IL</span>&#44; interleucina&#59; <span class="elsevierStyleItalic">TNF</span>&#44; fator de necrose tumoral&#59; <span class="elsevierStyleItalic">IFN</span>&#44; interferon&#59; <span class="elsevierStyleItalic">CS</span>&#44; controles saud&#225;veis&#59; <span class="elsevierStyleItalic">Sem</span>&#44; pacientes com psor&#237;ase sem uso de imunossupressores sist&#234;micos&#59; <span class="elsevierStyleItalic">Cl&#225;ssico</span>&#44; pacientes com psor&#237;ase em uso de imunossupressores cl&#225;ssicos&#59; <span class="elsevierStyleItalic">&#945;&#8208;TNF</span>&#44; pacientes com psor&#237;ase em uso de agentes antifator de necrose tumoral&#59; <span class="elsevierStyleItalic">&#945;&#8208;IL</span>&#44; pacientes com psor&#237;ase em uso de agentes anti&#8208;IL&#46; Os valores de p para todos os grupos que apresentaram diferen&#231;a significante s&#227;o mostrados na parte inferior de cada gr&#225;fico&#46; Valores de p n&#227;o significantes &#40;&#62; 0&#44;05&#41; n&#227;o s&#227;o representados&#46;</p>"
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">N&#237;veis s&#233;ricos de citocinas em pacientes com psor&#237;ase de acordo com a sobrevida do medicamento estratificada por 1 a 4 anos e 5 a 6 anos&#46; Os dados s&#227;o mostrados como distribui&#231;&#227;o de dispers&#227;o de valores individuais em gr&#225;ficos de barras representando n&#237;veis m&#233;dios de cada citocina&#46; IL&#44; interleucina&#59; TNF&#44; fator de necrose tumoral&#59; IFN&#44; interferon&#59; CS&#44; controles saud&#225;veis&#46; Os valores de p para todos os grupos que apresentaram diferen&#231;a significante s&#227;o mostrados na parte inferior de cada gr&#225;fico&#46; Valores de p n&#227;o significantes &#40;&#62; 0&#44;05&#41; n&#227;o s&#227;o representados&#46;</p>"
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          "pt" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de sobrevida mostrando o efeito conjunto dos dois principais preditores de interrup&#231;&#227;o da medica&#231;&#227;o&#58; a interleucina &#40;IL&#41;&#8208;6 e o &#205;ndice de Qualidade de Vida em Dermatologia &#40;DLQI&#41;&#46; Pode&#8208;se observar que os pacientes com n&#237;veis mais elevados de DLQI e IL&#8208;6 tiveram quase 75&#37; de chance de mudan&#231;a do tratamento sist&#234;mico no per&#237;odo de seguimento&#46; <span class="elsevierStyleItalic">mIL6</span>&#44; escores medianos de IL&#8208;6<span class="elsevierStyleHsp" style=""></span>da popula&#231;&#227;o atual &#40;0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo do valor mediano&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima do valor mediano&#41;&#46; <span class="elsevierStyleItalic">mDLQI</span>&#44; escore DLQI da popula&#231;&#227;o atual&#59; 0<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>abaixo de 5&#59; 1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>acima ou igual a 5&#46;</p>"
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                  \t\t\t\t">133 &#40;50&#44;76&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>F&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Idade&#58; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">H&#225;bito de tabagismo&#44; n&#160;&#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Abuso de &#225;lcool&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;2&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;4&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;6&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;10&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IL&#8208;17A&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de IFN&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">N&#237;veis de TNF&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Medicamentos associados&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Falhas terap&#234;uticas anteriores&#58; mediana &#40;IIQ&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Bioexclusivos&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Classifica&#231;&#227;o da psor&#237;ase</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Placas&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Couro cabeludo n &#40;&#37;&#41;&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\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ungueal n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\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 &#40;2&#44;86&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\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 &#40;1&#44;91&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Palmoplantar n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2 &#40;1&#44;64&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gutata n &#40;&#37;&#41;&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">5 &#40;4&#44;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">13 &#40;4&#44;96&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Invertida n &#40;&#37;&#41;&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">1 &#40;0&#44;82&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1 &#40;0&#44;71&#37;&#41;&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">2 &#40;0&#44;76&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \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
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                  \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
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                  \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"><span class="elsevierStyleBold">ASC basal&#44; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">12&#44;65 &#40;18&#44;71&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">8&#44;17 &#40;16&#44;00&#41;</span>&nbsp;\t\t\t\t\t\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
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;056</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&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"><span class="elsevierStyleBold">PASI basal&#44; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">5&#44;66 &#40;6&#44;58&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;01 &#40;6&#44;02&#41;</span>&nbsp;\t\t\t\t\t\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;038</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;99 &#40;0&#44;96&#8211;1&#44;03&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;739</span>&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"><span class="elsevierStyleBold">DLQI basal&#44; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">7&#44;57 &#40;7&#44;79&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">4&#44;42 &#40;6&#44;10&#41;</span>&nbsp;\t\t\t\t\t\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">1&#44;04 &#40;1&#44;01&#8211;1&#44;07&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;012</span>&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"><span class="elsevierStyleBold">NAPSI basal&#44; m&#233;dia &#40;DP&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">3&#44;79 &#40;7&#44;76&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">1&#44;08 &#40;3&#44;50&#41;</span>&nbsp;\t\t\t\t\t\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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8211;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">1&#44;02 &#40;0&#44;99&#8211;1&#44;05&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;113</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3426280.png"
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Ponto de corte definido como resultado positivo ou negativo&#46;</p>"
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            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Ponto de corte definido como valor abaixo&#44; acima ou igual ao valor da mediana da popula&#231;&#227;o global&#46;</p>"
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise univariada e multivariada para preditores de interrup&#231;&#227;o de medicamento no tratamento da psor&#237;ase</p>"
        ]
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Article information
ISSN: 26662752
Original language: Portuguese
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