荷兰阿姆斯特丹大学医学中心Geert D’Haens团队研究了Mirikizumab诱导和维持治疗溃疡性结肠炎的疗效与安全性。2023年6月28日出版的《新英格兰医学杂志》发表了这项成果。

Mirikizumab是一种针对白细胞介素-23的p19定向抗体，在2期临床试验中显示出治疗溃疡性结肠炎的疗效。

研究组在患有中度至重度活动性溃疡性结肠炎的成年人中进行了两项3期、随机、双盲、安慰剂对照试验。在诱导试验中，患者以3:1的比例被随机分配接受Mirikizumab（300mg）或安慰剂，每4周静脉注射一次，持续12周。在维持试验中，对Mirikizumab诱导治疗有反应的患者以2:1的比例被随机分配接受Mirikizumab（200mg）或安慰剂治疗，每4周皮下给药一次，持续40周。主要终点是诱导试验第12周和维持试验第40周（总共52周）的临床缓解。关键次要终点包括临床缓解、内镜缓解和排便紧迫性改善。在诱导试验中没有缓解的患者被允许在维持试验的前12周接受开放标签的Mirikizumab作为延长诱导。还对安全性进行了评估。

在诱导试验中，共有1281名患者接受了随机分组，544名对Mirikizumab有缓解的患者在维持试验中再次接受了随机化。在诱导试验第12周（24.2%对13.3%，P＜0.001）和维持试验第40周（49.9%对25.1%，P＞0.001），Mirikizumab组的患者临床缓解率明显高于安慰剂组。两项试验均符合所有关键次要终点的标准。与安慰剂相比，Mirikizumab组更频繁地报告鼻咽炎和关节痛的不良事件。在这两个试验的对照期和非对照期（包括开放标签延长期和维持期）接受Mirikizumab治疗的1217名患者中，15名患者发生机会性感染（包括6名带状疱疹感染），8名患者有癌症（包括3名大肠癌）。在诱导试验中接受安慰剂的患者中，有1名患者感染带状疱疹，没有一名患者患有癌症。

研究结果表明，Mirikizumab在诱导和维持中度至重度活动性溃疡性结肠炎患者的临床缓解方面比安慰剂更有效。少数接受Mirikizumab治疗的患者发生了机会感染或癌症。

附：英文原文

Title: Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis

Author: Geert D’Haens, M.D., Ph.D.,, Marla Dubinsky, M.D.,, Taku Kobayashi, M.D., Ph.D.,, Peter M. Irving, M.D.,, Stefanie Howaldt, M.D.,, Juris Pokrotnieks, M.D., Ph.D.,, Kathryn Krueger, M.D.,, Janelle Laskowski, Ph.D.,, Xingyuan Li, Ph.D.,, Trevor Lissoos, M.D.,, Joe Milata, B.S.N.,, Nathan Morris, Ph.D.,, Vipin Arora, Ph.D.,, Catherine Milch, M.D.,, William Sandborn, M.D.,, and Bruce E. Sands, M.D.

Issue&Volume: 2023-06-28

Abstract:

Background

Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.

Methods

We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed.

Results

A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P