Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials.

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
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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 new safety risks 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.

Trial registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135.

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利桑单抗治疗溃疡性结肠炎:两项随机临床试验
重要性:利坦珠单抗(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:目的:评估利坦珠单抗作为溃疡性结肠炎患者的诱导和维持疗法的疗效和安全性:进行了两项 3 期随机临床试验。诱导试验在全球41个国家的261个临床中心进行,从2020年11月5日到2022年8月4日招募了977名患者(2023年5月16日进行最后随访)。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)。符合条件的患者均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、先进疗法或两种疗法均有不耐受或反应不充分的病史;既往未接触过利桑单抗:在诱导试验中,患者按 2:1 随机分配,在第 0、4 和 8 周静脉注射 1200 毫克利桑珠单抗或安慰剂。在维持试验中,静脉注射利坦珠单抗后出现临床应答(使用改良的梅奥评分确定)的患者按1:1:1的比例随机分配,在52周内每8周皮下注射180毫克或360毫克利坦珠单抗或安慰剂(不再接受利坦珠单抗治疗):主要结果是诱导试验第12周和维持试验第52周时的临床缓解(大便次数评分≤1且不高于基线,直肠出血评分为0,内镜子评分≤1且无易碎性):在接受诱导试验分析的 975 名患者中(年龄 42.1 [SD, 13.8] 岁;男性 586/973 [60.1%];白人 677 [69.6%]),1200 毫克利桑珠单抗的第 12 周临床缓解率为 132/650 (20.3%),安慰剂为 20/325 (6.2%)(调整后组间差异为 14.0% [95% CI, 10.0%-18.0%], P 结论和相关性:与安慰剂相比,利桑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。需要进一步研究以确定52周随访后的疗效:试验注册:ClinicalTrials.gov Identifiers:试验注册:ClinicalTrials.gov Identifiers:NCT03398148 和 NCT03398135。
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期刊介绍: JAMA, published continuously since 1883, is an international peer-reviewed general medical journal. JAMA is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.
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