Reinisch Walter, Loftus Edward V, Schreiber Stefan, Rubin David T, Louis Edouard, Hecht Patrick M, Barrachina Elena Marced, Kalabic Jasmina, Vladea Ramona, Sharma Dolly, Duan Weijiang Rachel, Zhang Yafei, Panaccione Remo
Clinical Department of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.
J Crohns Colitis. 2025 Apr 4;19(4). doi: 10.1093/ecco-jcc/jjaf025.
This post hoc analysis evaluated the corticosteroid-sparing effects of risankizumab (RZB) therapy in patients with moderate-to-severe ulcerative colitis in the phase 3 induction and maintenance studies, INSPIRE and COMMAND.
Patients were randomized (2:1) to 12 weeks of intravenous RZB or placebo (PBO) induction therapy; responders to intravenous RZB were randomized (1:1:1) to receive subcutaneous RZB 180 mg, 360 mg, or PBO (RZB withdrawal) maintenance therapy. Baseline corticosteroid doses were maintained during induction, with a mandatory taper beginning at maintenance week 0. Efficacy outcomes were evaluated by baseline corticosteroid use at induction week 12, while corticosteroid-free clinical and endoscopic outcomes were assessed at maintenance week 52 among the overall population and among patients on corticosteroids at baseline. Safety was also assessed.
At baseline, 35.7% (348/975) of patients were taking corticosteroids. At induction week 12, greater rates were observed for clinical, endoscopic, and patient-reported outcomes in RZB 1200 mg-treated patients compared with PBO, regardless of baseline corticosteroid use. RZB 180 mg and 360 mg treatment resulted in higher corticosteroid discontinuation rates (RZB 180 mg 64.9% [48/74]; RZB 360 mg 54.2% [32/59]; PBO [withdrawal] 36.8% [25/68], P ≤ .01) and corticosteroid-free clinical, endoscopic, and patient-reported outcomes at week 52, compared with PBO (withdrawal). The rates of treatment-emergent adverse events were similar regardless of baseline corticosteroid use during induction and maintenance.
The efficacy of RZB induction therapy was independent of corticosteroid use, with high rates of corticosteroid-free outcomes observed in the overall population and among patients with baseline corticosteroid use, reaffirming the potential of RZB to serve as a corticosteroid-sparing therapy for patients with ulcerative colitis.
CLINICALTRIAL.GOV NUMBERS: NCT03398148 and NCT03398135.
这项事后分析评估了瑞莎珠单抗（RZB）在3期诱导和维持研究INSPIRE和COMMAND中对中度至重度溃疡性结肠炎患者的糖皮质激素节省效应。
患者被随机（2:1）分为接受12周静脉注射RZB或安慰剂（PBO）诱导治疗；静脉注射RZB的应答者被随机（1:1:1）接受皮下注射RZB 180mg、360mg或PBO（RZB撤药）维持治疗。诱导期间维持基线糖皮质激素剂量，从维持第0周开始强制减量。疗效结果通过诱导第12周时的基线糖皮质激素使用情况进行评估，而在总体人群以及基线时使用糖皮质激素的患者中，在维持第52周评估无糖皮质激素的临床和内镜结果。同时也评估了安全性。
基线时，35.7%（348/975）的患者正在使用糖皮质激素。在诱导第12周时，与PBO相比，接受1200mg RZB治疗的患者在临床、内镜和患者报告结局方面的发生率更高，无论基线时是否使用糖皮质激素。与PBO（撤药）相比，180mg和360mg RZB治疗导致更高的糖皮质激素停药率（180mg RZB 64.9%[48/74]；360mg RZB 54.2%[32/59]；PBO[撤药]36.8%[25/68]，P≤0.01）以及在第52周时无糖皮质激素的临床、内镜和患者报告结局。无论诱导和维持期间基线时是否使用糖皮质激素，治疗中出现的不良事件发生率相似。
RZB诱导治疗的疗效与糖皮质激素使用无关，在总体人群以及基线时使用糖皮质激素的患者中均观察到高比例的无糖皮质激素结局，再次证实了RZB作为溃疡性结肠炎患者糖皮质激素节省疗法的潜力。
NCT03398148和NCT03398135。
