Cholapranee A, Hazlewood G S, Kaplan G G, Peyrin-Biroulet L, Ananthakrishnan A N
Department of Internal Medicine, Montefiore Medical Center, New York, NY, USA.
Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
Aliment Pharmacol Ther. 2017 May;45(10):1291-1302. doi: 10.1111/apt.14030. Epub 2017 Mar 22.
Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome.
To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis.
We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis.
A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC.
Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.
黏膜愈合是克罗恩病（CD）和溃疡性结肠炎（UC）治疗中的一个重要治疗终点。关于各种疗法在实现这一结果方面的比较疗效的数据有限。
对用于诱导和维持克罗恩病及溃疡性结肠炎黏膜愈合的生物制剂进行系统评价和荟萃分析。
我们对随机对照试验（RCT）进行了系统评价和荟萃分析，这些试验将黏膜愈合作为中度至重度CD或UC免疫抑制剂、抗肿瘤坏死因子α（抗TNF）或抗整合素单克隆抗体治疗的终点。计算诱导和维持黏膜愈合的合并效应量，并使用贝叶斯网络荟萃分析评估成对治疗比较。
荟萃分析共纳入12项RCT（CD - 2项诱导试验，4项维持试验；UC - 8项诱导试验，5项维持试验）。诱导试验的随访时间为6 - 12周，维持试验为32 - 54周。在CD中，抗TNF药物在维持黏膜愈合方面比安慰剂更有效[28%对1%，优势比（OR）19.71，95%置信区间（CI）3.51 - 110.84]。在UC中，抗TNF药物和抗整合素在诱导（45%对30%）和维持黏膜愈合（33%对18%）方面比安慰剂更有效。在网络分析中，在UC诱导黏膜愈合方面，阿达木单抗治疗不如英夫利昔单抗[OR 0.45，95%可信区间（CrI）0.25 - 0.82]和英夫利昔单抗 - 硫唑嘌呤联合治疗（OR 0.32，95% CrI 0.12 - 0.84）。在UC中，维多珠单抗和抗TNF药物之间没有统计学上的显著成对差异。
抗TNF和抗整合素生物制剂在诱导UC黏膜愈合方面有效，阿达木单抗不如英夫利昔单抗或联合治疗。在CD中，英夫利昔单抗和阿达木单抗相似。
