美国梅奥诊所Edward V. Loftus团队研究了瑞莎珠单抗治疗溃疡性结肠炎的疗效与安全性。这一研究成果发表在2024年7月22日出版的《美国医学会杂志》上。

瑞莎珠单抗（一种选择性靶向IL-23 p19亚基的单克隆抗体）治疗溃疡性结肠炎的临床效果尚不清楚。

为了评价瑞莎珠单抗作为溃疡性结肠炎患者诱导和维持治疗的有效性和安全性，研究组进行了两项3期随机临床试验。诱导试验在261个临床中心（41个国家）进行，从2020年11月5日到2022年8月4日招募了977名患者（最终随访于2023年5月16日）。维持试验在238个临床中心（37个国家）进行，从2018年8月28日到2022年3月30日招募了754名患者（最终随访时间为2023年4月11日）。符合条件的患者患有中度至重度活动性溃疡性结肠炎；对一种或多种常规疗法、高级疗法或两种疗法都有不耐受或反应不足的病史；之前未接触过瑞莎珠单抗。

在诱导试验中，患者以2:1的比例随机分配，在第0、4和8周静脉注射1200 mg瑞莎珠单抗或安慰剂。在维持试验中，静脉注射瑞莎珠单抗后出现临床缓解（使用改良的Mayo评分确定）的患者被随机分配为1:1:1，每8周接受180 mg或360 mg瑞莎珠单抗或安慰剂（不再接受瑞莎珠单抗）的皮下治疗，持续52周。主要结局为诱导试验第12周和维持试验第52周的临床缓解（大便频率评分≤1且不大于基线，直肠出血评分为0，内镜评分≤1，且无易损性）。

在诱导试验中分析的975名患者中（年龄42.1[SD，13.8]岁；586/973名[60.1%]为男性；677名[69.6%]为白人），1200 mg瑞莎珠单抗组在第12周的临床缓解率为132/650（20.3%），安慰剂组为20/325（6.2%）（调整组间差异，14.0%[95%CI，10.0%-18.0%]，P<0.001）。在维持试验中分析的548名患者中（年龄40.9[SD，14.0]岁；313名[57.1%]为男性；407名[74.3%]为白人），180 mg瑞莎珠单抗组第52周的临床缓解率为72/179（40.2%），360 mg瑞莎珠单抗组为70/186（37.6%），安慰剂组为46/183（25.1%）（调整180 mg瑞莎珠单抗与安慰剂的组间差异，16.3%[97.5%CI，6.1%-26.6%]，P<0.001；360 mg瑞莎珠单抗与安慰剂的组间差异调整后为14.2%[97.5%CI，4.0%-24.5%]，P=0.002）。治疗组未检测到不良事件信号。

研究结果表明，与安慰剂相比，瑞莎珠单抗在中度至重度活动性溃疡性结肠炎患者的诱导试验和维持试验中提高了临床缓解率。仍需要进一步的研究来确定52周随访后的益处。

附：英文原文

Title: Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials

Author: Edouard Louis, Stefan Schreiber, Remo Panaccione, Peter Bossuyt, Luc Biedermann, Jean-Frederic Colombel, Gareth Parkes, Laurent Peyrin-Biroulet, Geert D’Haens, Tadakazu Hisamatsu, Britta Siegmund, Kaichun Wu, Brigid S. Boland, Gil Y. Melmed, Alessandro Armuzzi, Phillip Levine, Jasmina Kalabic, Su Chen, Ling Cheng, Lei Shu, W. Rachel Duan, Valerie Pivorunas, Yuri Sanchez Gonzalez, Ronilda D’Cunha, Ezequiel Neimark, Kori Wallace, Raja Atreya, Marc Ferrante, Edward V. Loftus, INSPIRE and COMMAND Study Group, Domingo Balderramo, Silvina Goncalves, Juan Lasa, Abel Novillo, Orlando Ruffinengo, Sonja Heeren, Walter Reinisch, Filip Baert, Peter Bossuyt, Arnaud Colard, Olivier Dewit, Marc Ferrante, Denis Franchimont, Edouard Louis, Jean-Francois Rahier, Carlos Francesconi, Roberto Kaiser Junior, Rogerio Parra, Ligia Sassaki, Plamen Penchev, Desislav Stanchev, Kenneth Atkinson, Melanie Beaton, Talat Bessissow, Susan Greenbloom, Jean-Rene Lachance, Allen Lim, Remo Panaccione, Jean- Michel Samson, Scott Shulman, Jesse Siffledeen, Ignacio Alfaro, Carlos Valenzuela, Gustavo Walsen, Ping An, Qian Cao, Yan Chen, Youxiang Chen, Xiang Gao, Xiaohua Hou, Naizhong Hu, YAN Li, Fei Liu, Mei Liu, Lu Lungen

Issue&Volume: 2024-07-22

Abstract:

Importance  The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.

Objective  To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.

Design, Setting, and Participants  Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab.

Interventions  For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks.

Main Outcomes and Measures  The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial.

Results  Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P<.001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P<.001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P=.002). No adverse event signals were detected in the treatment groups.

Conclusion and Relevance  Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up.

DOI: 10.1001/jama.2024.12414

Source: https://jamanetwork.com/journals/jama/fullarticle/2821291