Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment

IF 12 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Clinical Gastroenterology and Hepatology Pub Date : 2025-10-01 Epub Date: 2025-02-03 DOI:10.1016/j.cgh.2024.12.023

Remo Panaccione , Marc Ferrante , Iris Dotan , Julian Panés , Tadakazu Hisamatsu , Peter Bossuyt , Silvio Danese , Alexandra Song , Jasmina Kalabic , Namita Joshi , Javier Zambrano , Yafei Zhang , W. Rachel Duan , Kristina Kligys , Marla C. Dubinsky , James O. Lindsay , Severine Vermeire , Britta Siegmund , Peter M. Irving , Geert D’Haens

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Abstract

Background & Aims

The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn’s disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment (‘initial nonresponders’).

Methods

Initial nonresponders to intravenous (IV) RZB induction (600 mg or 1200 mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200 mg IV at W12, W16, and W20, or subcutaneous [SC] 180 mg or 360 mg at W12 and W20). Patients with clinical response to SC RZB at W24 (‘delayed responders’) continued their dose in FORTIFY. Clinical, endoscopic, and safety outcomes were evaluated.

Results

Most initial nonresponders achieved stool frequency (SF)/ abdominal pain score (APS) clinical response by W24 (76.2% [180 mg SC], 63.7% [360 mg SC], 62.3% [1200 mg IV]), whereas a subset also achieved W24 SF/APS clinical remission (43.0%, 45.1%, and 22.1%), endoscopic response (32.4%, 32.5%, and 40.5%), and endoscopic remission (25.1%, 18.0%, and 23.5%). Most delayed responders to SC RZB continued to demonstrate clinical response at FORTIFY W52 (56.7% [180 mg SC], 69.7% [360 mg SC]), along with SF/APS clinical remission (43.3% and 54.5%), endoscopic response (36.7% and 45.5%), and endoscopic remission (40.0% and 42.4%). Numerically greater efficacy was generally observed with 360 mg SC vs 180 mg SC. The safety profile of extended treatment was consistent with previously reported trials.

Conclusions

Most initial nonresponders to IV RZB induction who received 12W of extended RZB treatment demonstrated improved clinical and endoscopic outcomes at W24. Improvements in patients who received SC RZB extended treatment were maintained during FORTIFY. Extended treatment was well tolerated with no new safety risks identified.

ClinicalTrials.gov: MOTIVATE (Number: NCT03104413), ADVANCE (Number: NCT03105128), and FORTIFY (Number: NCT03105102).

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延长利桑单抗治疗对诱导治疗未达到临床反应的克罗恩病患者

背景和目的：在中度至重度克罗恩病（CD）患者中，对12周(W) RZB诱导治疗（“初始无反应”）未达到临床反应的患者，采用抗白细胞介素- 23p19单克隆抗体risankizumab （RZB）延长治疗的有效性和安全性进行了评估。方法：最初对静脉（IV） RZB诱导（W0、W4和W8时分别为600mg或1200mg）无反应的患者以1:1:1重新随机分组，接受延长的RZB盲法治疗（W12、W16和W20时分别为1200mg静脉注射，W12和W20时分别为180mg或360mg皮下注射）。在W24（“延迟反应”）时对SC RZB有临床反应的患者继续服用FORTIFY。评估临床、内窥镜和安全性结果。结果：大多数初始无应答者通过W24获得SF/APS临床缓解（76.2% [180mg SC], 63.7% [360mg SC], 62.3% [1200mg IV]），而一小部分患者也获得了W24 SF/APS临床缓解（43.0%,45.1%,22.1%），内镜缓解（32.4%,32.5%,40.5%）和内镜缓解（25.1%,18.0%,23.5%）。大多数SC RZB延迟应答者在FORTIFY W52下继续表现出临床应答（56.7% [180mg SC], 69.7% [360mg SC]）， SF/APS临床缓解（43.3%,54.5%），内镜下缓解（36.7%,45.5%）和内镜下缓解（40.0%,42.4%）。从数值上看，360mg SC比180mg SC更有效。延长治疗的安全性与先前报道的试验一致。结论：大多数最初对静脉RZB诱导无反应的接受12W延长RZB治疗的患者在W24时表现出改善的临床和内镜结果。接受SC RZB延长治疗的患者在FORTIFY期间保持了改善。延长治疗耐受性良好，未发现新的安全风险。

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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.