The Efficacy and Safety of Etrasimod in Mildly to Moderately Active Ulcerative Colitis: Results From the Phase II GLADIATOR Trial.

BACKGROUND & AIMS: Etrasimod is an approved, oral, once-daily, selective sphingosine 1-phosphate receptor modulator with efficacy and safety in moderately to severely active ulcerative colitis demonstrated in the ELEVATE UC program. GLADIATOR evaluated etrasimod efficacy and safety in adults with mildly to moderately active ulcerative colitis.

METHODS

GLADIATOR was a phase II, double-blind, treat-through trial. Patients with baseline modified Mayo score 4 to 6, endoscopic subscore ≥2, and rectal bleeding subscore ≥1 were randomized (2:1; stratified by biologic/Janus kinase inhibitor experience and baseline corticosteroid use) to etrasimod 2 mg or placebo once daily (52 weeks). The primary endpoint was the proportion of patients achieving clinical remission at week 52. Safety was assessed throughout in all randomized patients receiving ≥1 study treatment dose. Pooled post hoc phase III ELEVATE UC modified Mayo score 4 to 6 subpopulation data were also analyzed.

RESULTS

GLADIATOR's primary endpoint was not met, although a numerically greater proportion of patients receiving etrasimod vs placebo achieved clinical remission at week 52 (26.0% vs 18.3%; placebo-adjusted percentage difference: 7.4; 95% confidence interval, -5.2 to 19.9; P = .25). In the similar ELEVATE UC subpopulation, more patients receiving etrasimod vs placebo achieved clinical remission at week 52. Etrasimod was generally well-tolerated; safety findings were consistent with the known safety profile.

CONCLUSIONS

Despite GLADIATOR not meeting its primary endpoint, the totality of modified Mayo score 4 to 6 population data from GLADIATOR and ELEVATE UC reiterates the positive benefit-risk profile of etrasimod in active ulcerative colitis, while providing insights for clinical practice and future studies in mildly to moderately active ulcerative colitis.

CLINICALTRIALS: gov, Numbers: NCT04607837, NCT03945188, NCT03996369, NCT04706793.