Impact of Extended Risankizumab Treatment in Patients With Ulcerative Colitis Who Did Not Respond to Induction Treatment.

IF 12 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Clinical Gastroenterology and Hepatology Pub Date : 2025-09-13 DOI:10.1016/j.cgh.2025.09.007

Remo Panaccione, Gil Y Melmed, David Drobne, Manreet Kaur, Silvio Danese, Tadakazu Hisamatsu, Jasmina Kalabic, Su Chen, Ling Cheng, W Rachel Duan, Saajan Shah, Edouard Louis

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引用次数: 0

Abstract

Background & aims: The efficacy and safety of extended induction treatment with risankizumab, an interleukin-23 p19 inhibitor, in patients with moderately to severely active ulcerative colitis (UC) who, per site evaluation, did not achieve clinical response to 12 weeks of risankizumab induction was evaluated.

Methods: In the phase 3 INSPIRE induction study, 209 initial nonresponders to 12 weeks of 1200 mg intravenous (IV) risankizumab induction were rerandomized to receive 12 weeks of additional 1200 mg risankizumab (weeks 12, 16, and 20) or 180 mg or 360 mg subcutaneous [SC] risankizumab (weeks 12 and 20) in a double-blind fashion. Patients from both phase 2b and 3 with week 24 clinical response to SC risankizumab (delayed responders) continued to receive blinded risankizumab at their assigned dose in the phase 3 COMMAND maintenance study. Efficacy and safety were evaluated at week 24 of induction and week 52 of maintenance.

Results: Initial nonresponders (1200 mg IV [n = 68], 180 mg SC [n = 71], or 360 mg SC [n = 70]) had week 24 clinical response rates of 50%, 56.3%, and 57.1%, respectively; patients also achieved clinical remission, histologic endoscopic mucosal improvement (8.8%, 12.7%, and 15.7% for both endpoints), endoscopic improvement (17.6%, 18.3%, and 24.3%), and endoscopic remission (1.5%, 8.5%, and 5.7%). Efficacy rates were generally highest with 360 mg. In maintenance, delayed responders demonstrated sustained rates of clinical remission and increased rates of endoscopic outcomes and histologic endoscopic mucosal improvement at week 52. The safety with extended risankizumab treatment was consistent with the known risankizumab safety profile.

Conclusions: Over 50% of initial nonresponders achieved clinical response with extended risankizumab treatment. Additional clinical and endoscopic outcomes were also achieved, with sustained or improved efficacy observed following maintenance. Extended treatment was well tolerated with no new safety risks identified. ClincialTrials.gov, Numbers. NCT03398148 (INSPIRE), NCT03398135 (COMMAND).

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延长利桑单抗治疗对诱导治疗无效的溃疡性结肠炎患者的影响

背景和目的：对中度至重度活动性溃疡性结肠炎（UC）患者进行延长诱导治疗（一种白细胞介素23p19抑制剂）的有效性和安全性进行了评估，这些患者在每个部位的评估中，在12周(W)的利桑单抗诱导治疗中没有达到临床反应。方法：在3期INSPIRE诱导研究中，209例最初对12W 1200mg静脉（IV）瑞桑单抗诱导无反应的患者被重新随机分组，以双盲方式接受12W额外的1200mg瑞桑单抗（W12、W16和W20）或180mg或360mg皮下（SC）瑞桑单抗（W12和W20）。在3期COMMAND维持研究中，对SC利桑单抗临床反应为W24（延迟反应）的2b期和3期患者继续接受指定剂量的利桑单抗盲法治疗。在诱导W24和维持W52时评估疗效和安全性。结果：初始无反应（1200mg IV [n=68], 180mg SC [n=71]，或360mg SC [n=70]）的W24临床缓解率分别为50%，56.3%和57.1%；患者也达到了临床缓解、组织学内镜下粘膜改善（HEMI）（8.8%、12.7%、15.7%，两个终点）、内镜下改善（17.6%、18.3%、24.3%）和内镜下缓解（1.5%、8.5%、5.7%）。360mg时疗效最高。在维持治疗中，延迟应答者表现出持续的临床缓解率，并在W52时增加了内窥镜结果和HEMI的发生率。延长risankizumab治疗的安全性与已知的risankizumab安全性一致。结论：超过50%的初始无应答者在延长利桑单抗治疗后达到临床应答。其他临床和内窥镜结果也得到了实现，在维持后观察到持续或改善的疗效。延长治疗耐受性良好，未发现新的安全风险；ClincialTrials.gov编号，NCT03398148 (INSPIRE), NCT03398135 （COMMAND）。

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来源期刊

Clinical Gastroenterology and Hepatology 医学-胃肠肝病学

CiteScore

16.90

自引率

4.80%

发文量

903

审稿时长

22 days

期刊介绍： Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion. As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.