维得利珠单抗治疗慢性袋炎。

Vedolizumab for the Treatment of Chronic Pouchitis.

机构信息

From the Translational Gastroenterology Unit and Kennedy Institute, National Institute for Health and Care Research Oxford Biomedical Research Centre, University of Oxford, Oxford (S.T.), and the Inflammatory Bowel Disease Unit, St. Mark's Hospital and Imperial College London, London (A.H.) - both in the United Kingdom; the Division of Gastroenterology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto (M.S.S.), the Department of Medicine, Division of Gastroenterology, Western University (V.J.), and Alimentiv (V.J., B.G.F.), London, ON, and the Department of Medicine, Division of Gastroenterology, University of British Columbia, Vancouver (B.B.) - all in Canada; the Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan (S.D.), and the Inflammatory Bowel Disease Unit, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna (P.G.) - both in Italy; the Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam (M.L.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium (M.F.); Takeda Pharmaceuticals International, Zurich, Switzerland (D.L., A.E., S.J.); and the Interventional Inflammatory Bowel Disease Center and the Center for Ileal Pouch Disorders, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York (B.S.).

出版信息

N Engl J Med. 2023 Mar 30;388(13):1191-1200. doi: 10.1056/NEJMoa2208450.

DOI:10.1056/NEJMoa2208450

Abstract

BACKGROUND

Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis.

METHODS

We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings.

RESULTS

Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group.

CONCLUSIONS

Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).

摘要

背景

大约一半接受回肠储袋肛管吻合术（IPAA）的溃疡性结肠炎患者随后会发生储袋炎，其中五分之一会患有慢性储袋炎。

方法

我们进行了一项 4 期、双盲、随机试验，以评估 vedolizumab 在接受 IPAA 治疗溃疡性结肠炎后发生慢性储袋炎的成年患者中的疗效。患者以 1:1 的比例随机分配接受 vedolizumab 静脉注射，剂量为 300mg，或安慰剂，分别于第 1 天和第 2、6、14、22 和 30 天给药。所有患者在第 1 周到第 4 周同时接受环丙沙星治疗。主要终点是改良储袋炎疾病活动指数（mPDAI）定义的缓解（mPDAI 评分≤4 分，mPDAI 总分较基线降低≥2 分；评分范围为 0 至 12 分，分数越高表示储袋炎越严重），在第 14 周评估。mPDAI 基于临床症状和内镜检查结果。其他疗效终点包括第 34 周时 mPDAI 定义的缓解、第 14 周和第 34 周时 mPDAI 定义的应答（mPDAI 评分较基线降低≥2 分）以及第 14 周和第 34 周时 PDAI 定义的缓解（PDAI 评分≤6 分，较基线降低≥3 分；评分范围为 0 至 18 分，分数越高表示储袋炎越严重）。PDAI 基于临床症状、内镜检查结果和组织学检查结果。

结果

在 102 名接受随机分组的患者中，vedolizumab 组第 14 周时 mPDAI 定义的缓解率为 31%（51 例患者中的 16 例），安慰剂组为 10%（51 例患者中的 5 例）（差异为 21 个百分点；95%置信区间 [CI]，5 至 38；P=0.01）。vedolizumab 组在第 34 周时 mPDAI 定义的缓解率、第 14 周和第 34 周时 mPDAI 定义的应答率（差异分别为 17 个百分点、30 个百分点）以及第 14 周和第 34 周时 PDAI 定义的缓解率（差异分别为 25 个百分点、22 个百分点）方面也均优于安慰剂组。95%CI，8 至 41）和第 34 周时（差异为 19 个百分点；95%CI，2 至 40）以及第 14 周时 PDAI 定义的缓解率（差异为 25 个百分点；95%CI，8 至 41）和第 34 周时（差异为 19 个百分点；95%CI，2 至 37）。vedolizumab 组有 3 例（6%）患者和安慰剂组有 4 例（8%）患者发生严重不良事件。