背景:造瘘性克罗恩病(CD)的医学治疗仍然是临床医生面临的挑战。在过去的20年里,生物疗法一直是造瘘性CD的医学治疗的主要手段。这项研究的目的是比较生物疗法在诱导CD的反应和缓解方面的功效。
方法:我们对EMBASE进行了系统评价,MEDLINE,和CochraneCentral数据库从成立到2021年12月。纳入标准是任何随机对照试验(RCT),该试验评估了生物疗法对活性比较剂或安慰剂的疗效,以诱导患有CD的成年人的反应或缓解。瘘管反应或缓解的患者比例,根据每个临床试验的定义,是我们的主要研究结果。使用贝叶斯随机效应网络荟萃分析来衡量治疗效果,并将结果报告为优势比(OR)和95%置信区间(CI)。
结果:在我们的分析中,包括10项研究,都是RCT.英夫利昔单抗在诱导反应方面优于阿达木单抗(OR,0.24;95%CI,0.06-0.99),但不诱导缓解(OR,0.31;95%CI,0.04-2.27)。肿瘤坏死因子拮抗剂在诱导反应方面优于安慰剂(OR,0.51;95%CI,0.35-0.750)和缓解(OR,0.36;95%CI,0.22-0.58)。英夫利昔单抗在诱导反应方面优于安慰剂(OR,0.36;95%CI,0.17-0.75)和缓解(OR,0.17;95%CI,0.03-0.87)。Ustekinumab在诱导反应方面优于安慰剂(OR,0.48;95%CI,0.26-0.860),但不诱导缓解(OR,0.50;95%CI,0.13-1.93)。当生物疗法相互比较时,诱导缓解无统计学差异。维多珠单抗在诱导缓解方面并不优于安慰剂(OR,0.32;95%CI,0.04-2.29)。Certolizumab在诱导反应方面并不优于安慰剂(OR,0.78;95%CI,0.40-1.55)或缓解(OR,0.78;95%CI,0.40-1.55)。
结论:肿瘤坏死因子拮抗剂可有效诱导CD流成病的反应和缓解。英夫利昔单抗诱导反应优于阿达木单抗,但不诱导缓解。Ustekinumab对诱导反应有效,但对诱导缓解无效。当彼此比较时,生物疗法在诱导缓解方面没有显着差异。根据现有数据,英夫利昔单抗是首选的一线治疗方案.至于其他生物制品,有限的公布数据不允许我们提出坚定的建议。这项研究支持当前的实践,并强调需要专门的RCT来评估生物疗法在造骨CD中的疗效。
尽管生物治疗的时代,克罗恩病的治疗仍然具有挑战性.这是第一个系统评价和网络荟萃分析,以比较生物疗法在诱导克罗恩病患者的反应和缓解中的功效。我们发现抗肿瘤坏死因子剂可有效诱导反应和缓解。英夫利昔单抗诱导反应优于阿达木单抗,但不诱导缓解。
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.
Despite the era of biologic therapies, the management of fistulizing
Crohn’s disease remains challenging. This is the first systematic
review and network meta-analysis to compare the efficacy of biologic therapies in inducing response and remission in patients with fistulizing
Crohn’s disease. We found that anti-tumor necrosis factor agents are effective in inducing response and remission. Infliximab was superior to adalimumab for inducing response but not for inducing remission.