Hart Ailsa, Panaccione Remo, Steinwurz Flavio, Danese Silvio, Hisamatsu Tadakazu, Cao Qian, Ritter Timothy, Seidler Ursula, Olurinde Mobolaji, Vetter Marion L, Yee Jacqueline, Yang Zijiang, Wang Yuhua, Johanns Jewel, Han Chenglong, Sahoo Aparna, Terry Natalie A, Sands Bruce E, D'Haens Geert
London North-West University Healthcare NHS Trust, London, United Kingdom.
University of Calgary, Calgary, Alberta, Canada.
Gastroenterology. 2025 Aug;169(2):308-325. doi: 10.1053/j.gastro.2025.02.033. Epub 2025 Mar 18.
BACKGROUND & AIMS: Subcutaneous (SC) induction and maintenance with guselkumab was evaluated in adult participants with moderately to severely active Crohn's disease.
The Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400 mg SC every 4 weeks→100 mg SC every 8 weeks (n = 115), guselkumab 400 mg SC every 4 weeks→200 mg SC every 4 weeks (n = 115), or placebo (n = 117). Placebo participants meeting rescue criteria received guselkumab from week 16 onward. Co-primary endpoints were clinical remission at week 12 and endoscopic response at week 12. Additional multiplicity-controlled endpoints were Patient-Reported Outcome-2 remission (week 12), clinical response (week 12), clinical remission (week 24), clinical remission (week 48), and endoscopic response (week 48). Safety was assessed through week 48.
All multiplicity-controlled endpoints were met. At week 12, significantly greater proportions of participants receiving guselkumab 400 mg achieved clinical remission vs placebo (56.1% vs 21.4%; Δ = 34.9; P < .001), and endoscopic response vs placebo (41.3% vs 21.4%; Δ = 19.9; P < .001). At week 48, significantly greater proportions of participants in both guselkumab groups (100 mg SC every 8 weeks: 60.0%, Δ = 42.8; 200 mg SC every 4 weeks: 66.1%, Δ = 48.9) achieved clinical remission vs placebo (17.1%; P < .001 each) and endoscopic response (44.3%, Δ = 37.5; 51.3%, Δ = 44.6; vs placebo 6.8%; P < .001 each). Efficacy was observed in both bionaive participants and those with inadequate response or intolerance to biologics. Adverse event rates were not greater in guselkumab groups vs placebo.
Subcutaneous guselkumab for both induction and maintenance was efficacious in treating participants with moderately to severely active Crohn's disease. Safety findings were consistent with those of guselkumab in approved indications, including ulcerative colitis. (ClinicalTrials.gov, Number: NCT05197049.).
在中度至重度活动性克罗恩病成年参与者中评估了古塞库单抗的皮下诱导和维持治疗效果。
3期双盲、安慰剂对照、全程治疗的GRAVITI研究将347名参与者按1:1:1随机分为三组，分别接受每4周皮下注射400mg古塞库单抗→每8周皮下注射100mg（n = 115）、每4周皮下注射400mg古塞库单抗→每4周皮下注射200mg（n = 115）或安慰剂（n = 117）。符合救援标准的安慰剂组参与者从第16周起接受古塞库单抗治疗。共同主要终点为第12周的临床缓解和第12周的内镜反应。其他多重控制终点为患者报告结局-2缓解（第12周）、临床反应（第12周）、临床缓解（第24周）、临床缓解（第48周）和内镜反应（第48周）。安全性评估至第48周。
所有多重控制终点均达到。在第12周时，接受400mg古塞库单抗治疗的参与者实现临床缓解的比例显著高于安慰剂组（56.1%对21.4%；差异=34.9；P<.001），实现内镜反应的比例也高于安慰剂组（41.3%对21.4%；差异=19.9；P<.001）。在第48周时，两个古塞库单抗组的参与者实现临床缓解的比例均显著高于安慰剂组（每8周皮下注射100mg：60.0%，差异=42.8；每4周皮下注射200mg：66.1%，差异=48.9）（安慰剂组为17.1%；每组P<.001），实现内镜反应的比例也更高（44.3%，差异=37.5；51.3%，差异=44.6；安慰剂组为6.8%；每组P<.001）。在初治参与者以及对生物制剂反应不足或不耐受的参与者中均观察到了疗效。古塞库单抗组的不良事件发生率不高于安慰剂组。
皮下注射古塞库单抗用于诱导和维持治疗对中度至重度活动性克罗恩病参与者有效。安全性结果与古塞库单抗在包括溃疡性结肠炎在内的已批准适应症中的结果一致。（ClinicalTrials.gov编号：NCT05197049。）
