Estudo clínico controlado não-randomizado para avaliação da efetividade clínica e endoscópica na Doença de Crohn: Infliximabe versus Adalimumabe

• Main Author: Baima, Júlio Pinheiro [UNESP]
• Other Authors: Universidade Estadual Paulista (UNESP)
• Language: Portuguese
• Published: Universidade Estadual Paulista (UNESP) 2018
• Subjects: Doença de Crohn; Terapia Biológica; resposta clínica; resposta endoscópica; Crohn's disease; biological therapy; clinical response; endoscopic response
• Online Access: http://hdl.handle.net/11449/153774

Submitted by JÚLIO PINHEIRO BAIMA ([e-mail]) on 2018-04-25T20:09:46Z No. of bitstreams: 1 Tese Doutorado Julio Pinheiro Baima 25 abril 2018.pdf: 1976761 bytes, checksum: fade6f9adcb14ae4ad0854e9274f5c9d (MD5) === Approved for entry into archive by Sulamita Selma C Colnago null ([e-mail]) on 2018-04-26T19:04:00Z (GMT) No. of bitstreams: 1 baima_jp_dr_bot_int.pdf: 1976761 bytes, checksum: fade6f9adcb14ae4ad0854e9274f5c9d (MD5) === Made available in DSpace on 2018-04-26T19:04:00Z (GMT). No. of bitstreams: 1 baima_jp_dr_bot_int.pdf: 1976761 bytes, checksum: fade6f9adcb14ae4ad0854e9274f5c9d (MD5) Previous issue date: 2018-02-27 === Introdução: Com o advento da terapia biológica, o foco de resposta na Doença de Crohn (DC) ampliou-se, sendo essenciais a remissão clínica e endoscópica. Estudos prospectivos comparando os representantes dessa classe terapêutica mais utilizados, o Infliximabe (IFX) e o Adalimumabe (ADA), são escassos. O objetivo do estudo foi comparar a efetividade clínica e endoscópica do IFX versus ADA em pacientes com DC naïves terapia biológica, na semana 54 de tratamento. Metodologia: Foi realizado um estudo clínico, não-randomizado, no qual pacientes com DC que receberam IFX ou ADA, foram avaliados nas semanas 0, 14, 30 e 54 de tratamento. Utilizou-se o Índice de Atividade da Doença de Crohn (CDAI) para avaliação da atividade clínica da doença. Entre 6 e 12 meses, foi avaliada a atividade endoscópica através do Simplified Endoscopic Score for Crohn’s Disease (SES-CD). As variáveis foram resposta clínica (queda do CDAI > 70 pontos) e remissão clínica (CDAI < 150 pontos), avaliados nas semanas 14, 30 e 54, e resposta endoscópica (queda do SES-CD de pelo menos 50% em relação à pontuação inicial), remissão endoscópica (controle endoscópico com SES-CD ≤ 2 pontos), e taxas de internação, cirurgia, óbito e perda de resposta, analisados na semana 54. A análise estatística foi estatística descritiva, teste de ANOVA com medidas repetidas no tempo considerando a interação medicamento x tempo, seguida do teste de comparação múltipla de Tukey ajustado, com nível de significância de 5% ou o p-valor correspondente. Resultados: Foram incluídos 85 pacientes, 45 submetidos ao tratamento com ADA e 40 com IFX. O uso concomitante de Azatioprina foi mais frequente no grupo que recebeu IFX (p=0,0001). As taxas de resposta clínica foram de 86,67% na semana 14, 82,22% na semana 30 e 82,22% na semana 54 no grupo ADA. No grupo IFX, as taxas de resposta foram 70%, 72,5% e 75%, respectivamente, sem diferença entre os tratamentos (p>0,05 em todas as semanas). As taxas de remissão clínica no grupo ADA foram de 86,67% na semana 14, 80% na semana 30 e 82,22% na Resumo 3 semana 54. No grupo IFX, 65%, 62,5% e 65% respectivamente, com diferença significativa apenas na semana 14 (p=0,02). Resposta endoscópica foi atingida em 60,61% dos pacientes do grupo ADA e 85,71% no grupo IFX (p=0,02). As taxas de remissão endoscópica foram de 45,45% e 60%, respectivamente (p=0,23). Internações, cirurgia, óbitos e perda de resposta ocorreram com frequência sem diferença significativa entre os grupos. Conclusões: Não houve diferença nas taxas de resposta clínica entre os tratamentos. Houve maiores taxas de remissão clínica na semana 14 no grupo ADA, não mantidas nas semanas seguintes. Taxas de resposta endoscópica foram melhores no grupo IFX. Não houve diferença nas taxas de remissão endoscópica. Não houve diferença nas taxas de internações, cirurgias e óbitos, assim como na perda de resposta. === Introduction: With the advent of biological therapy, the focus of the Crohn's Disease (CD) response has changed and clinical and endoscopic remission are essential. Prospective studies comparing the most used biological drugs, Infliximab (IFX) and Adalimumab (ADA), are scarce. Our aim was compare the clinical and endoscopic effectiveness of IFX versus ADA in CD patients naïve to biological therapy at the 54th week of treatment. Methods: An open, non-randomized, clinical study with CD patients receiving IFX or ADA was performed at treatment weeks 0, 14, 30 and 54. The Crohn's Disease Activity Index (CDAI) was used to evaluate the disease clinical activity. Between 6 and 12 months, colonoscopy was performed and the Simplified Endoscopic Score for Crohn's Disease (SES-CD) was used. Clinical response (CDAI decrease>70 points) and clinical remission (CDAI<150 points) were assessed at weeks 14, 30 and 54; endoscopic response (decrease of at least 50% in SES-CD), endoscopic remission (endoscopic control with SES-CD ≤ 2 points), and hospitalization rates, surgeries, deaths and loss of response, were analyzed at week 54. A statistical analysis was descriptive with ANOVA test with repeated measures considering drug interaction x time, followed by Tukey multiple comparison test adjusted, with a significance level of 5% or the corresponding p-value. Results: A total of 85 patients were included, 45 patients underwent treatment with ADA and 40 with IFX, with difference between groups only in concomitant use of azathioprine, more frequent in the IFX group (p=0.0001). Clinical response rates were 86.67% at week 14, 82.22% at week 30 and 82.22% at week 54 in ADA group. In IFX group, 70%, 72.5% and 75%, respectively (p> 0.05 on all weeks). Clinical remission rates were 86.67% at week 14, 80% at week 30 and 82.22% at week 54 in ADA group. In IFX group, 65%, 62.5% and 65%, respectively, with significate difference only at week 14 (p = 0.02). Endoscopic response rate was 60.61% in patients from ADA group and 85.71% in the IFX group (p = 0.02). Rates of Abstract 6 endoscopic remission were 45.45% and 60%, respectively (p = 0.23). Hospitalizations, surgery, deaths and loss of lost response occurred without significant difference between groups. Conclusions: There were no difference in the clinical response rates between treatments. There was higher rate of clinical remission at week 14 in the ADA group, not sustained in the subsequent weeks. Endoscopic response rate was better in the IFX group. There was no difference in endoscopic remission rate. There were no difference in hospitalization rates, surgeries and deaths, as well as loss of response.