Comparative Effectiveness of Immunosuppressants and Biologics for Inducing and Maintaining Remission in Crohn's Disease: A Network Meta-analysis
Comparative Effectiveness of Immunosuppressants and Biologics for Inducing and Maintaining Remission in Crohn's Disease: A Network Meta-analysis
复制标题
DOI：
10.1053/j.gastro.2014.10.011
复制
发表时间：
2015-02-01
期刊：
影响因子：
29.4
通讯作者：
Kaplan, Gilaad G.
中科院分区：
文献类型：
--
作者：
Hazlewood, Glen S.;Rezaie, Ali;Kaplan, Gilaad G.
背景与目的：由于缺乏直接的比较试验，关于克罗恩病患者的最佳治疗存在争议。基于直接和间接证据，我们比较了诱导和维持克罗恩病患者缓解的治疗方法。方法：截至2014年6月，我们对MEDLINE、EMBASE和Cochrane Central数据库进行了系统评价。我们确定了随机对照试验（N = 39），比较甲氨喋呤、硫唑嘌呤/6-巯基嘌呤、英夫利昔单抗、阿达木单抗、certolizumab、vedolizumab或联合治疗与安慰剂或活性药物诱导和维持克罗恩病成年患者缓解的疗效。通过贝叶斯随机效应网络荟萃分析估计两两治疗效果，并以95%可信区间（CrI）的优势比（OR）报告。结果：英夫利昔单抗、英夫利昔单抗联合硫唑嘌呤（英夫利昔单抗+硫唑嘌呤）、阿达木单抗和维多单抗在诱导缓解方面优于安慰剂。在抗肿瘤坏死因子药物的两两比较中，英夫利昔单抗+硫唑嘧啶（OR, 3.1; 95% CrI, 1.4-7.7）和阿达木单抗（OR, 2.1; 95% CrI, 1.0-4.6）在诱导缓解方面优于certolizumab。除了英夫利昔单抗和甲氨蝶呤联合使用外，所有治疗在维持缓解方面都优于安慰剂。阿达木单抗、英夫利昔单抗和英夫利昔单抗+硫唑嘌呤优于硫唑嘌呤/6-巯基嘌呤：阿达木单抗（OR, 2.9; 95% CrI, 1.6-5.1）、英夫利昔单抗（OR, 1.6; 95% CrI, 1.0-2.5）、英夫利昔单抗+硫唑嘌呤（OR, 3.0; 95% CrI, 1.7-5.5）维持缓解。阿达木单抗和英夫利昔单抗+硫唑嘌呤优于certolizumab：阿达木单抗（OR, 2.5; 95% CrI, 1.4-4.6）和英夫利昔单抗+硫唑嘌呤（OR, 2.6; 95% CrI, 1.3-6.0）。阿达木单抗优于维多单抗（OR, 2.4; 95% CrI, 1.2-4.6）。结论：基于网络荟萃分析，阿达木单抗和英夫利昔单抗+硫唑嘌呤是诱导和维持克罗恩病缓解最有效的治疗方法。
BACKGROUND & AIMS: There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence. METHODS: We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). RESULTS: Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pairwise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6). CONCLUSIONS: Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease.