Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn's Disease: Results From the Phase 3 GRAVITI Study.

Methods

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).

第三阶段的双盲、安慰剂对照、持续治疗GRAVITI研究将347名参与者随机分为1:1:1三组，分别接受guselkumab 400 mg SC每4周一次→100 mg SC每8周一次（n = 115），guselkumab 400 mg SC每4周一次→200 mg SC每4周一次（n = 115），或安慰剂（n = 117）。

Placebo participants meeting rescue criteria received guselkumab from week 16 onward.

符合救援标准的安慰剂参与者从第16周开始接受guselkumab治疗。

Co-primary endpoints were clinical remission at week 12 and endoscopic response at week 12.

主要共研究终点是第12周的临床缓解和第12周的内镜反应。

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).

额外的多重性控制终点包括患者报告结果-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）。

Safety was assessed through week 48.

安全性评估持续到第48周。

Results

All multiplicity-controlled endpoints were met.

所有多重性控制的终点均得到满足。

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).

在第12周，接受guselkumab 400 mg治疗的参与者中，与安慰剂相比，达到临床缓解的比例显著更高（56.1%对比21.4%；差异Δ = 34.9；P < .001），以及内镜下反应的比例也显著高于安慰剂（41.3%对比21.4%；差异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).

在第48周时，与安慰剂组相比（临床缓解：17.1%；内镜反应：6.8%），接受guselkumab治疗的两组患者（每8周皮下注射100 mg组：临床缓解60.0%，Δ = 42.8；每4周皮下注射200 mg组：临床缓解66.1%，Δ = 48.9；内镜反应44.3%，Δ = 37.5；51.3%，Δ = 44.6）有显著更高的比例实现了临床缓解（P < .001）和内镜反应（P < .001）。

Efficacy was observed in both bionaive participants and those with inadequate response or intolerance to biologics.

无论是在生物制剂治疗史为阴性的参与者中，还是在对生物制剂反应不足或不耐受的参与者中，都观察到了guselkumab的疗效。

Adverse eventrates were not greater in guselkumab groups vs placebo.

不良事件发生率在guselkumab组与安慰剂组之间没有显著差异。

Conclusions

Subcutaneous guselkumab for both induction and maintenance was efficacious in treating participants with moderately to severely active Crohn's disease.

皮下注射guselkumab在诱导和维持治疗中对中度至重度活动性克罗恩病患者均显示出疗效。

Safety findings were consistent with those of guselkumab in approved indications, including ulcerative colitis.

安全性发现与古塞尔库单抗在批准的适应症中的发现一致，包括溃疡性结肠炎。

(ClinicalTrials.gov, Number: NCT05197049.).

(ClinicalTrials.gov, 编号: NCT05197049.)。