Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Gastroenterology. 2015 Feb;148(2):344-54.e5; quiz e14-5. doi: 10.1053/j.gastro.2014.10.011. Epub 2014 Oct 16.
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.
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).
Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise 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).
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.
由于缺乏直接比较试验，因此对于克罗恩病患者的最佳治疗方法存在争议。我们基于直接和间接证据比较了克罗恩病患者诱导和维持缓解的治疗方法。
我们通过 2014 年 6 月对 MEDLINE、EMBASE 和 Cochrane 中央数据库进行了系统评价。我们确定了 39 项比较甲氨蝶呤、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用于诱导和维持成人克罗恩病缓解的随机对照试验。通过贝叶斯随机效应网络荟萃分析估计了两两治疗效果，并以比值比（OR）和 95%可信区间（CrI）表示。
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 vedolizumab 诱导缓解优于安慰剂。在抗 TNF 药物的两两比较中，英夫利昔单抗+硫唑嘌呤（OR，3.1；95% CrI，1.4-7.7）和阿达木单抗（OR，2.1；95% CrI，1.0-4.6）诱导缓解优于 certolizumab。所有治疗方法维持缓解均优于安慰剂，除了英夫利昔单抗联合甲氨蝶呤。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）。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 vedolizumab（OR，2.4；95% CrI，1.2-4.6）。
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。
