Division of Gastroenterology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
Clin Gastroenterol Hepatol. 2012 Sep;10(9):1002-7; quiz e78. doi: 10.1016/j.cgh.2012.02.004. Epub 2012 Feb 15.
BACKGROUND & AIMS: Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD.
We performed a retrospective cohort study of adult patients with moderate-severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population.
Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03).
Most patients with moderate-severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.
多项随机对照试验（RCT）已开展，旨在确定生物制剂治疗炎症性肠病（IBD）的疗效。然而，由于严格的入选标准，RCT 研究结果的外部有效性可能会受到影响。本研究旨在调查在常规临床实践中遇到的患者中，有多少比例符合 IBD 生物制剂关键 RCT 的入选标准。
我们对就诊于三级转诊中心的中重度 IBD 成年患者进行了回顾性队列研究。从已发表的获得食品和药物管理局批准的生物制剂 RCT 中提取入选和排除标准，并应用于研究人群。
206 例 IBD 患者（34%为克罗恩病[CD]，26%为溃疡性结肠炎）中仅有 31.1%符合任何一项入选 RCT 的标准。患者因狭窄或穿透性 CD、高剂量类固醇治疗、合并症或既往使用生物制剂、或接受局部治疗而被排除在外。在溃疡性结肠炎中，23.3%的不符合 RCT 标准的患者接受了结肠切除术，31.7%接受了英夫利昔单抗治疗，缓解率为 63.2%。在 82 例不符合 CD 标准的患者中，约有一半（49.4%）接受了生物治疗，但缓解率（60%）低于符合 RCT 标准的患者（89%；P =.03）。
在门诊实践中评估的大多数中重度 IBD 患者不符合生物试剂关键 RCT 的入选标准；这一发现对 RCT 人群之外的治疗疗效提出了重要问题。需要进一步评估 RCT 设计和入选标准的透明度，以确定试验结果是否可以推广到人群。
