Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkabeer University Hospital, Aljabreyah, Kuwait.
Department of Public Health, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
Inflamm Bowel Dis. 2023 Mar 1;29(3):367-375. doi: 10.1093/ibd/izac103.
The medical treatment of fistulizing Crohn's disease (CD) remains a challenge to clinicians. Over the last 20 years, biologic therapies have been the mainstay of medical treatment of fistulizing CD. The purpose of this study is to compare the efficacy of biologic therapies in inducing response and remission in fistulizing CD.
We performed a systematic review of the EMBASE, MEDLINE, and Cochrane Central databases from inception to December 2021. Inclusion criteria were any randomized controlled trials (RCTs) that evaluated the efficacy of biologic therapies against an active comparator or placebo for induction of response or remission in adults with fistulizing CD. The proportion of patients with fistula response or remission, as defined by each clinical trial, was our primary study outcome. A Bayesian random-effects network meta-analysis was used to measure treatment effects and results were reported as odds ratio (OR) and 95% confidence interval (CI).
In our analysis, 10 studies were included, and all were RCTs. Infliximab was superior to adalimumab in inducing response (OR, 0.24; 95% CI, 0.06-0.99) but not in inducing remission (OR, 0.31; 95% CI, 0.04-2.27). Tumor necrosis factor antagonists were superior to placebo in the induction of response (OR, 0.51; 95% CI, 0.35-0.750) and remission (OR, 0.36; 95% CI, 0.22-0.58). Infliximab was superior to placebo in inducing response (OR, 0.36; 95% CI, 0.17-0.75) and remission (OR, 0.17; 95% CI, 0.03-0.87). Ustekinumab was superior to placebo in inducing response (OR, 0.48; 95% CI, 0.26-0.860) but not in inducing remission (OR, 0.50; 95% CI, 0.13-1.93). When comparing biologic therapies against each other, there was no statistical difference in inducing remission. Vedolizumab was not superior to placebo in inducing remission (OR, 0.32; 95% CI, 0.04-2.29). Certolizumab was not superior to placebo in inducing response (OR, 0.78; 95% CI, 0.40-1.55) or remission (OR, 0.78; 95% CI, 0.40-1.55).
Tumor necrosis factor antagonists are effective in inducing response and remission in fistulizing CD. Infliximab was superior to adalimumab for inducing response but not for inducing remission. Ustekinumab is effective in the induction of response but not in the induction of remission. When compared against each other, biologic therapies showed no significant difference in the induction of remission. Based on the available data, infliximab is the preferred first-line treatment. As for other biologics, the limited published data do not allow us to make firm recommendations. This study supports current practice and emphasizes the need for dedicated RCTs to evaluate the efficacy of biologic therapies in fistulizing CD.
瘘管性克罗恩病（CD）的治疗仍然是临床医生面临的挑战。在过去的 20 年中，生物疗法一直是瘘管性 CD 治疗的主要方法。本研究旨在比较生物疗法在诱导瘘管性 CD 缓解和缓解方面的疗效。
我们对 EMBASE、MEDLINE 和 Cochrane Central 数据库进行了系统回顾，检索时间从成立到 2021 年 12 月。纳入标准为任何评价生物疗法与活性对照或安慰剂在诱导瘘管性 CD 缓解和缓解方面疗效的随机对照试验（RCT）。每个临床试验定义的瘘管反应或缓解患者的比例是我们的主要研究结果。采用贝叶斯随机效应网络荟萃分析来衡量治疗效果，结果以比值比（OR）和 95%置信区间（CI）表示。
在我们的分析中，纳入了 10 项研究，均为 RCT。英夫利昔单抗在诱导缓解方面优于阿达木单抗（OR，0.24；95%CI，0.06-0.99），但在诱导缓解方面无差异（OR，0.31；95%CI，0.04-2.27）。肿瘤坏死因子拮抗剂在诱导缓解（OR，0.51；95%CI，0.35-0.750）和缓解（OR，0.36；95%CI，0.22-0.58）方面优于安慰剂。英夫利昔单抗在诱导缓解（OR，0.36；95%CI，0.17-0.75）和缓解（OR，0.17；95%CI，0.03-0.87）方面优于安慰剂。乌司奴单抗在诱导缓解方面优于安慰剂（OR，0.48；95%CI，0.26-0.860），但在诱导缓解方面无差异（OR，0.50；95%CI，0.13-1.93）。比较生物疗法之间的差异，在诱导缓解方面无统计学差异。维得利珠单抗在诱导缓解方面不优于安慰剂（OR，0.32；95%CI，0.04-2.29）。培塞利珠单抗在诱导缓解（OR，0.78；95%CI，0.40-1.55）或缓解（OR，0.78；95%CI，0.40-1.55）方面不优于安慰剂。
肿瘤坏死因子拮抗剂在诱导瘘管性 CD 缓解和缓解方面有效。英夫利昔单抗在诱导缓解方面优于阿达木单抗，但在诱导缓解方面无差异。乌司奴单抗在诱导缓解方面有效，但在诱导缓解方面无差异。比较生物疗法之间的差异，在诱导缓解方面无统计学差异。基于现有数据，英夫利昔单抗是首选的一线治疗药物。至于其他生物制剂，有限的已发表数据还不允许我们做出明确的推荐。本研究支持当前的实践，并强调需要进行专门的 RCT 来评估生物疗法在瘘管性 CD 中的疗效。
