Subcutaneous induction therapy with guselkumab in Crohn's disease (GRAVITI)
Subcutaneous induction therapy with guselkumab in Crohn's disease (GRAVITI)
Subcutaneous induction and maintenance therapy with the IL-23 antibody guselkumab was significantly more effective than placebo in a phase 3 trial enrolling patients with moderately to severely active Crohn's disease and achieved comparable clinical outcomes as in previous trials with intravenous induction therapy.
Background and aims: Subcutaneous (SC) induction and maintenance with guselkumab was evaluated in adult participants with moderately to severely active Crohn's disease.
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). 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 400 mg achieved clinical remission vs. placebo (56.1% vs. 21.4%; Δ = 34.9; p < 0.001), and endoscopic response vs. placebo (41.3% vs. 21.4%; Δ = 19.9; p < 0.001). 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 < 0.001 each) and endoscopic response (44.3%, Δ = 37.5; 51.3%, Δ = 44.6; vs. placebo 6.8%; p < 0.001 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.
Conclusion: 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.