Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; Robarts Clinical Trials Inc, London, Ontario, Canada.
Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
Clin Gastroenterol Hepatol. 2018 Nov;16(11):1714-1729.e3. doi: 10.1016/j.cgh.2018.06.005. Epub 2018 Jun 14.
BACKGROUND & AIMS: Agents are being developed for treatment of eosinophilic esophagitis (EoE). However, it is not clear what outcome measures would best determine the efficacy and safety of these agents in clinical trials. We performed a systematic review of outcomes used in randomized placebo-controlled trials of EoE and we estimate the placebo response and rates of remission.
We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register from inception through February 20, 2018 for randomized controlled trials of pharmacologic therapies for EoE. Efficacy outcome definitions, measurement tools, and the proportion of patients responding to placebo were collected and stratified by based on histologic, endoscopic, and patient-reported outcomes.
We analyzed data from 22 placebo-controlled trials, comprising 1112 patients with EoE. Ten additional active registered trials were identified. Most published trials evaluated topical corticosteroid therapy (13/22, 59.1%). Histologic outcomes measuring eosinophil density and patient-reported outcomes were reported in 21/22 published trials (95.5%). No consistently applied definitions of histologic or patient-reported response or remission were identified. Endoscopic outcomes were described in 60% (12/20) of published trials. The EoE Endoscopic Reference Score is the most commonly applied tool for describing changes in endoscopic appearance. The median histologic response to placebo was 3.7% (range, 0%-31.6%) and the median rate of remission in patients given placebo was 0.0% (range, 0%-11.0%). The median patient-reported response to placebo was 14.4% (range, 8.6%-77.8%) and rate of remission in patients given placebo was 26.2% (range, 13.2%-35.7%).
In a systematic review of the literature, we found that no standardized definitions of histologic, endoscopic, or patient-reported outcomes are used to determine whether pharmacologic agents produce a response or remission in patients with EoE. A core outcome set is needed to reduce heterogeneity in outcome reporting and facilitate trial interpretation and comparison of results from trials.
目前正在开发用于治疗嗜酸性食管炎（EoE）的药物。然而，目前尚不清楚哪种疗效评估方法最适合评估这些药物在临床试验中的疗效和安全性。本研究旨在对 EoE 的随机安慰剂对照试验中的疗效评估方法进行系统评价，并估计安慰剂的反应和缓解率。
我们检索了 MEDLINE、Embase、CENTRAL、ClinicalTrials.gov 和欧盟临床试验注册库，检索时间从建库至 2018 年 2 月 20 日，以查找治疗 EoE 的药物治疗的随机对照试验。收集疗效评估结果定义、测量工具和对安慰剂有反应的患者比例，并根据组织学、内镜和患者报告的结果进行分层。
我们分析了 22 项安慰剂对照试验的数据，共纳入 1112 例 EoE 患者。另外还确定了 10 项正在进行的活性药物对照试验。发表的大多数试验评估了局部皮质类固醇治疗（13/22，59.1%）。21/22 项发表的试验（95.5%）报告了组织学评估结果（测量嗜酸性粒细胞密度）和患者报告的结果。没有确定组织学或患者报告的反应或缓解的一致应用定义。60%（12/20）的发表试验描述了内镜评估结果。EoE 内镜参考评分是最常用于描述内镜表现变化的工具。安慰剂组的组织学反应中位数为 3.7%（范围：0%-31.6%），安慰剂组患者的缓解率中位数为 0.0%（范围：0%-11.0%）。安慰剂组患者报告的反应中位数为 14.4%（范围：8.6%-77.8%），安慰剂组患者的缓解率中位数为 26.2%（范围：13.2%-35.7%）。
在对文献的系统评价中，我们发现没有标准化的组织学、内镜或患者报告的结果定义用于确定药物治疗是否能使 EoE 患者产生反应或缓解。需要制定一个核心结局集，以减少结局报告的异质性，并促进试验解释和对试验结果的比较。
