DOP063 Etrasimod efficacy in patients with mildly to moderately active Ulcerative Colitis: pooled results from the ELEVATE UC and GLADIATOR trials

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis (UC). Limited data exist for advanced therapies in patients with mildly to moderately active UC. This pooled, post-hoc analysis evaluated the efficacy of etrasimod versus placebo in patients with mildly to moderately active UC, as defined by a modified Mayo score of 4–6, an endoscopic subscore ≥2 and a rectal bleeding subscore ≥1. Methods Data were pooled from patients randomised to etrasimod 2 mg QD or placebo in the GLADIATOR clinical trial and a prespecified subpopulation with mildly to moderately active UC in ELEVATE UC 52, ELEVATE UC 12 and ELEVATE UC 40 JAPAN trials. Efficacy endpoints of clinical remission, endoscopic improvement, symptomatic remission and endoscopic improvement-histologic remission (EIHR) were assessed at Week 12 and Week 52; sustained clinical remission and corticosteroid (CS)-free clinical remission were assessed at Week 52. Results In this pooled population, 348 patients received etrasimod and 169 received placebo. Baseline characteristics were generally balanced between treatment arms (Table). Significantly greater proportions of patients receiving etrasimod versus placebo achieved all endpoints at both Week 12 and Week 52, including clinical remission (Week 12: 36.2% vs 16.0%; Week 52: 34.2% vs 15.4%; all p<0.001), endoscopic improvement (Week 12: 48.0% vs 22.5%; Week 52: 41.5% vs 21.1%; all p<0.001), symptomatic remission (Week 12: 47.4% vs 29.6%: p<0.001; Week 52: 42.3% vs 27.6%: p = 0.004) and EIHR (Week 12: 29.9% vs 10.7%; Week 52: 31.9% vs 15.4%; all p<0.001). The same was observed for sustained clinical remission (22.7% vs 7.3%; p<0.001) and CS-free clinical remission (33.8% vs 13.8%; p<0.001; Figure) at Week 52. Safety in the GLADIATOR trial and the subpopulation of patients from the ELEVATE UC clinical programme with mildly to moderately active UC was consistent with the known safety profile of etrasimod. Conclusion In this pooled analysis, etrasimod demonstrated efficacy in the treatment of patients with mildly to moderately active UC, adding evidence to support the efficacy of etrasimod across the spectrum of active UC. References: Disclaimer: Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content. Conflict of interest: Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Dubinsky, Marla C: Consulting fees from: AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Johnson & Johnson, Merck, Pfizer Inc, Prometheus Biosciences, Prometheus Laboratories, Sanofi, Sphyre, Takeda, and UCB Shareholder/Royalties in: Trellus Health Directorship/Ownership interest in: Trellus Health. Yarur, Andres: Consultancy fees from: AbbVie, Arena, Bristol Myers Squibb, Celltrion, Pfizer Inc, and Takeda Lecture fees from: AbbVie and Bristol Myers Squibb. Walsh, Alissa: Grant/Research support from: AbbVie, Alfasigma, Bristol Myers Squibb, Buhlmann, Eli-Lilly, Falk, Galapagos, Janssen, Pfizer Inc, Sandoz, Takeda, and Tillotts. Wosik, Karolina: Employee of Pfizer Canada and shareholder of Pfizer Inc. Woolcott, John: Employee and shareholder of Pfizer Inc. Lazin, Krisztina: Employee of Pfizer AG and shareholder of Pfizer Inc. Zang, Chuanbo: Employee and shareholder of Pfizer Inc. Wang, Wenjin: Employee and shareholder of Pfizer Inc. Menon, Sujatha: Employee and shareholder of Pfizer Inc. Goetsch, Martina: Employee of Pfizer AG and shareholder of Pfizer Inc. Danese, Silvio: Consultancy/Advisory fees from: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB, and Vifor Lecture/Speaker fees from: AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer Inc, and Takeda Directorship/Ownership in: Gastroenterology and Endoscopy.