Robarts Clinical Trials, Western University, London, Ontario, Canada; Department of Medicine, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada.
UCSD Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, California; Robarts West, La Jolla, California.
Gastroenterology. 2013 Jul;145(1):149-157.e2. doi: 10.1053/j.gastro.2013.03.025. Epub 2013 Mar 22.
BACKGROUND & AIMS: Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations.
We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6.
The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P = .011).
Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.
溃疡性结肠炎（UC）试验中，内镜评估的观察者间差异导致安慰剂反应率的变化。我们研究了集中审查图像是否可以减少这些差异。
我们进行了一项为期 10 周、随机、双盲、安慰剂对照的研究，共纳入 281 例轻度至中度活动期 UC 患者，UC 活动指数（UCDAI）直肠镜评分≥2，评估了延迟释放美沙拉嗪（Asacol 4.8g/天）的疗效。内镜图像由一位专家中心读者进行评估。主要结局是第 6 周的临床缓解（UCDAI 中，粪便频率和出血评分均为 0，无粪便紧迫感）。
美沙拉嗪组 30.0%的患者达到主要结局，安慰剂组为 20.6%，差异为 9.4%（95%置信区间[CI]，-0.7%至 19.4%；P=0.069）。二次分析的显著差异表明美沙拉嗪的疗效。31%的参与者，所有参与者的 UCDAI 直肠镜评分均≥2，由现场研究者评估，但被中心读者认为不符合纳入标准。排除这些患者后，美沙拉嗪组和安慰剂组的缓解率分别为 29.0%和 13.8%（差异为 15%；95%CI，3.5%-26.0%；P=0.011）。
尽管基于意向治疗分析，美沙拉嗪 4.8g/天在诱导轻度至中度活动期 UC 患者缓解方面与安慰剂相比无统计学差异，但综合数据支持治疗有益。内镜图像的集中审查对于 UC 的诱导研究至关重要；临床试验注册号：NCT01059344。
