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

Abstract

Background and Aims

Subcutaneous (SC) induction and maintenance with guselkumab was evaluated in adult participants with moderately to severely active Crohn’s disease (CD).

Methods

The Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400mg SC q4w→100mg SC every 8 weeks (q8w) (n=115), guselkumab 400mg SC every 4 weeks (q4w)→200mg SC q4w (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.

Results

All multiplicity-controlled endpoints were met. At week 12, significantly greater proportions of participants receiving guselkumab 400mg achieved clinical remission versus placebo (56.1% vs 21.4%; Δ=34.9; p<0.001), and endoscopic response versus placebo (41.3% vs 21.4%; Δ=19.9; p<0.001). At week 48, significantly greater proportions of participants in both guselkumab groups (100mg SC q8w: 60.0%, Δ=42.8; 200mg SC q4w: 66.1%, Δ=48.9) achieved clinical remission versus placebo (17.1%; p<0.001 each) and endoscopic response (44.3%, Δ=37.5; 51.3%, Δ=44.6; versus placebo 6.8%; p<0.001 each). Efficacy was observed in both bionaive participants and those with inadequate response/intolerance to biologics. Adverse event rates were not greater in guselkumab groups versus placebo.

Conclusion

Subcutaneous guselkumab for both induction and maintenance was efficacious in treating participants with moderately to severely active CD. Safety findings were consistent with those of guselkumab in approved indications, including ulcerative colitis.