古塞库单抗治疗克罗恩病：2期GALAXI-1研究的诱导结果
Guselkumab for the Treatment of Crohn's Disease: Induction Results From the Phase 2 GALAXI-1 Study.
作者信息
Sandborn William J, D'Haens Geert R, Reinisch Walter, Panés Julián, Chan Daphne, Gonzalez Susana, Weisel Kathleen, Germinaro Matthew, Frustaci Mary Ellen, Yang Zijiang, Adedokun Omoniyi J, Han Chenglong, Panaccione Remo, Hisamatsu Tadakazu, Danese Silvio, Rubin David T, Sands Bruce E, Afzali Anita, Andrews Jane M, Feagan Brian G
机构信息
University of California-San Diego, La Jolla, California.
Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
出版信息
Gastroenterology. 2022 May;162(6):1650-1664.e8. doi: 10.1053/j.gastro.2022.01.047. Epub 2022 Feb 5.
BACKGROUND & AIMS: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis. This study evaluated the efficacy and safety of guselkumab in patients with moderately to severely active Crohn's disease with inadequate response or intolerance to conventional or biologic therapy.
METHODS
GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. Change from baseline in Crohn's Disease Activity Index score (primary end point), clinical remission, clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, endoscopic response (major secondary end points), and safety in guselkumab-treated patients vs placebo were evaluated through week 12. Ustekinumab was a reference arm.
RESULTS
Of 309 patients evaluated, approximately 50% had disease refractory to prior biologic therapy. At week 12, significantly greater reductions in Crohn's Disease Activity Index from baseline (least squares means: 200 mg: -160.4, 600 mg: -138.9, and 1200 mg: -144.9 vs placebo: -36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo (Crohn's Disease Activity Index <150; 57.4%, 55.6%, and 45.9% vs 16.4%; all, P < .05). Greater proportions of patients receiving guselkumab achieved clinical response, Patient Reported Outcomes-2 remission, clinical-biomarker response, and endoscopic response at week 12 vs placebo. Efficacy of ustekinumab vs placebo was also demonstrated. Safety event rates were generally similar across treatment groups.
CONCLUSIONS
At week 12, all 3 dose regimens of guselkumab induced greater clinical and endoscopic improvements vs placebo, with a favorable safety profile.
CLINICALTRIALS
gov, Number: NCT03466411.
背景与目的
古塞库单抗是一种选择性p19白细胞介素-23拮抗剂，已被批准用于治疗斑块状银屑病和银屑病关节炎。本研究评估了古塞库单抗在对传统治疗或生物治疗反应不足或不耐受的中度至重度活动性克罗恩病患者中的疗效和安全性。
方法
GALAXI-1是一项2期双盲、安慰剂对照研究，将患者按1:1:1:1:1随机分为静脉注射200mg、600mg或1200mg古塞库单抗组，分别在第0、4和8周给药；静脉注射乌司奴单抗约6mg/kg在第0周，皮下注射90mg在第8周；或安慰剂组。评估至第12周时，古塞库单抗治疗组与安慰剂组患者的克罗恩病活动指数评分（主要终点）较基线的变化、临床缓解、临床反应、患者报告结局-2缓解、临床生物标志物反应、内镜反应（主要次要终点）及安全性。乌司奴单抗作为对照臂。
结果
在309例接受评估的患者中，约50%的患者对先前的生物治疗难治。在第12周时，各古塞库单抗组的克罗恩病活动指数较基线均有显著更大幅度的降低（最小二乘均值：200mg组：-160.4，600mg组：-138.9，1200mg组：-144.9，而安慰剂组为-36.2；均P<0.05），且各古塞库单抗组达到临床缓解的患者比例显著高于安慰剂组（克罗恩病活动指数<150；分别为57.4%、55.6%和45.9%，而安慰剂组为16.4%；均P<0.05）。在第12周时，接受古塞库单抗治疗的患者达到临床反应、患者报告结局-2缓解、临床生物标志物反应和内镜反应的比例高于安慰剂组。乌司奴单抗对比安慰剂的疗效也得到了证实。各治疗组的安全事件发生率总体相似。
结论
在第12周时，古塞库单抗的所有3种剂量方案与安慰剂相比均能诱导更大的临床和内镜改善，且安全性良好。
临床试验
美国国立医学图书馆临床试验注册平台，编号：NCT03466411
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