Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; Robarts Clinical Trials, Western University, London, Ontario, Canada.
University of Guelph, Guelph, Ontario, Canada.
Clin Gastroenterol Hepatol. 2018 Sep;16(9):1407-1419.e22. doi: 10.1016/j.cgh.2018.02.051. Epub 2018 Mar 27.
BACKGROUND & AIMS: Endpoints in randomized controlled trials (RCTs) of Crohn's disease (CD) are changing. We performed a systematic review of efficacy and safety outcomes reported in placebo-controlled RCTs of patients with CD.
We searched the MEDLINE, EMBASE, and the Cochrane Library through March 1, 2017 for placebo-controlled RCTs of adult patients with CD treated with aminosalicylates, immunomodulators, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were collected and stratified by decade of publication.
Our final analysis included 116 RCTs (81 induction, 44 maintenance, 7 postoperative prevention trials, comprising 27,263 patients). Clinical efficacy endpoints were reported in all trials; the most common endpoint was CD activity index score. We identified 38 unique definitions of clinical response or remission and 32 definitions of loss of response. Definitions of endoscopic response, remission, and endoscopic healing were also heterogeneous, evaluated using the CD endoscopic index of severity, the simple endoscopic score for CD, ulcer resolution, and Rutgeerts' Score for postoperative endoscopic appearance. Histologic outcomes were reported in 11.1% of induction trials, 2.3% of maintenance trials, and 14.3% of postoperative prevention trials. Biomarker outcomes were reported in 81.5% induction trials, 68.2% of maintenance trials, and 42.9% of postoperative prevention trials. Safety outcomes were reported in 93.8% of induction trials, 97.7% of maintenance trials, and 85.7% of postoperative prevention trials.
In this systematic review, we demonstrate heterogeneity in definitions of response and remission, and changes in outcomes reported in RCTs of CD. It is a priority to select a core set of outcomes to standardize efficacy and safety evaluation in trials of patients with CD.
克罗恩病（CD）的随机对照试验（RCT）的终点正在发生变化。我们对 CD 患者接受氨基水杨酸盐、免疫调节剂、皮质类固醇、生物制剂和口服小分子药物治疗的安慰剂对照 RCT 中报告的疗效和安全性结局进行了系统评价。
我们通过 MEDLINE、EMBASE 和 Cochrane Library 检索了截至 2017 年 3 月 1 日的成人 CD 患者接受氨基水杨酸盐、免疫调节剂、皮质类固醇、生物制剂和口服小分子药物治疗的安慰剂对照 RCT 研究，收集了疗效和安全性结局、定义和测量工具，并按发表年代进行分层。
我们的最终分析包括 116 项 RCT（81 项诱导治疗、44 项维持治疗、7 项术后预防试验，共 27263 例患者）。所有试验均报告了临床疗效结局；最常见的结局是 CD 活动指数评分。我们确定了 38 个独特的临床缓解或缓解定义和 32 个缓解失败定义。内镜缓解、缓解和内镜愈合的定义也存在异质性，使用 CD 内镜严重程度指数、简单 CD 内镜评分、溃疡愈合和 Rutgeerts 术后内镜外观评分进行评估。组织学结局在 11.1%的诱导试验、2.3%的维持试验和 14.3%的术后预防试验中报告。生物标志物结局在 81.5%的诱导试验、68.2%的维持试验和 42.9%的术后预防试验中报告。安全性结局在 93.8%的诱导试验、97.7%的维持试验和 85.7%的术后预防试验中报告。
在这项系统评价中，我们证明了 CD RCT 中缓解和缓解的定义以及报告结局的变化存在异质性。选择一套核心结局来标准化 CD 患者临床试验的疗效和安全性评估是当务之急。
