Department of Biostatistics, University of Liverpool, Liverpool, UK.
Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, UK.
Aliment Pharmacol Ther. 2019 Apr;49(8):978-996. doi: 10.1111/apt.15174. Epub 2019 Mar 3.
The suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation.
To undertake a systematic review of efficacy and safety outcomes in placebo-controlled randomised controlled trials (RCTs) of patients with Crohn's disease.
MEDLINE, EMBASE, CINAHL and Cochrane Library were searched until November 2015, for RCTs of adult Crohn's disease patients treated with medical or surgical therapies. Data on efficacy and safety outcomes, end-point definitions, and measurement instruments were extracted and stratified by publication date (pre-2009 and 2009 onwards).
One hundred and eighty-one RCTs (110 induction and 71 maintenance) were identified, including 23 850 patients. About 92.3% reported clinical efficacy endpoints. The Crohn's Disease Activity Index (CDAI) dominated, defining clinical response or remission in 63.5% of trials (35 definitions of response or remission). CDAI < 150 was the commonest endpoint, but reporting reduced between periods (46.4%-41.1%), whilst use of CDAI100 increased (16.8%-30.4%). Fistula studies most commonly reported fistula closure (9, 90.0%). Reporting of biomarker, endoscopy and histology endpoints increased overall (33.3%-40.6%, 14.4%-30.4% and 3.2%-12.5%, respectively), but were heterogeneous and rarely reported in fistula trials. Patient-reported outcome measures were reported in 41.4% of trials and safety endpoints in 35.4%. Many of the common adverse events relate to disease exacerbation or treatment failure.
Trial endpoints vary across studies, over time and are distinct in fistula studies. Despite growth in reporting of objective measures of inflammation and in patient-reported outcome measures, there is a lack of standardisation. This confirms the need for a core outcome set for comparative effectiveness research in Crohn's disease.
疾病活动指数的适用性受到了挑战，人们对炎症的客观衡量指标越来越感兴趣。
对克罗恩病患者的安慰剂对照随机对照试验（RCT）的疗效和安全性结果进行系统评价。
检索 MEDLINE、EMBASE、CINAHL 和 Cochrane Library，检索时间截至 2015 年 11 月，纳入接受药物或手术治疗的成年克罗恩病患者的 RCT。提取疗效和安全性结局、终点定义和测量仪器的数据，并按发表日期（2009 年之前和 2009 年之后）进行分层。
共纳入 181 项 RCT（110 项诱导治疗和 71 项维持治疗），共纳入 23850 例患者。约 92.3%的研究报告了临床疗效终点。克罗恩病活动指数（CDAI）占据主导地位，63.5%的试验（35 种缓解或缓解定义）用 CDAI 定义临床缓解或缓解。CDAI＜150 是最常见的终点，但报告在两个时期之间减少（46.4%-41.1%），而 CDAI100 的使用增加（16.8%-30.4%）。瘘管研究最常报告瘘管闭合（9 项，90.0%）。总体而言，生物标志物、内镜和组织学终点的报告有所增加（33.3%-40.6%、14.4%-30.4%和 3.2%-12.5%），但存在异质性，且在瘘管研究中很少报告。41.4%的试验报告了患者报告的结局，35.4%的试验报告了安全性结局。许多常见的不良事件与疾病恶化或治疗失败有关。
研究间、随时间推移，试验终点存在差异，瘘管研究中尤为明显。尽管炎症的客观测量指标和患者报告的结局测量指标的报告有所增加，但缺乏标准化。这证实了需要为克罗恩病的比较疗效研究制定一个核心结局集。
