Panaccione Remo, Ferrante Marc, Dotan Iris, Panés Julian, Hisamatsu Tadakazu, Bossuyt Peter, Danese Silvio, Song Alexandra, Kalabic Jasmina, Joshi Namita, Zambrano Javier, Zhang Yafei, Duan W Rachel, Kligys Kristina, Dubinsky Marla C, Lindsay James O, Vermeire Severine, Siegmund Britta, Irving Peter M, D'Haens Geert
Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Clin Gastroenterol Hepatol. 2025 Feb 3. doi: 10.1016/j.cgh.2024.12.023.
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').
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.
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.
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.
gov: MOTIVATE (Number: NCT03104413), ADVANCE (Number: NCT03105128), and FORTIFY (Number: NCT03105102).
在对12周的瑞莎珠单抗（RZB）诱导治疗未产生临床反应的中度至重度克罗恩病（CD）患者（“初始无反应者”）中，评估抗白细胞介素-23 p19单克隆抗体RZB延长治疗的疗效和安全性。
对静脉注射（IV）RZB诱导（第0周、第4周和第8周分别给予600mg或1200mg）无初始反应的患者，按1:1:1比例重新随机分组，接受延长的盲法RZB治疗（第12周、第16周和第20周静脉注射1200mg，或第12周和第20周皮下注射[SC]180mg或360mg）。在第24周对SC RZB有临床反应的患者（“延迟反应者”）在强化治疗中继续其剂量。评估临床、内镜和安全性结果。
大多数初始无反应者在第24周时达到了大便频率（SF）/腹痛评分（APS）临床反应（180mg SC组为76.2%，360mg SC组为63.7%，1200mg IV组为62.3%），而一部分患者在第24周时还实现了SF/APS临床缓解（分别为43.0%、45.1%和22.1%）、内镜反应（分别为32.4%、32.5%和40.5%）以及内镜缓解（分别为25.1%、18.0%和23.5%）。大多数对SC RZB延迟反应的患者在强化治疗第52周时仍表现出临床反应（180mg SC组为56.7%，360mg SC组为69.7%），同时伴有SF/APS临床缓解（分别为43.3%和54.5%）、内镜反应（分别为36.7%和45.5%）以及内镜缓解（分别为40.0%和42.4%）。一般观察到360mg SC组的疗效在数值上高于180mg SC组。延长治疗的安全性与先前报道的试验一致。
大多数接受12周RZB延长治疗的IV RZB诱导初始无反应者在第24周时临床和内镜结果得到改善。接受SC RZB延长治疗的患者在强化治疗期间维持了改善。延长治疗耐受性良好，未发现新的安全风险。
美国国立医学图书馆临床试验注册库：激励研究（编号：NCT03104413）、推进研究（编号：NCT03105128）和强化研究（编号：NCT03105102）。
