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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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