DOP062Efficacy of etrasimod in biologic/Janus kinase inhibitor-naïve patients with mildly to moderately active Ulcerative Colitis: results from the GLADIATOR trial

Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis (UC). No advanced therapies are currently approved for mildly to moderately active UC although there remains an unmet need, as many patients fail or are intolerant to conventional therapies. Prior exposure to biologic/Janus kinase inhibitor (bio/JAKi) therapy is often considered an indicator of greater disease severity in clinical practice. This prespecified subgroup analysis from the GLADIATOR trial evaluated the efficacy of etrasimod versus placebo in patients with mildly to moderately active UC, defined as a modified Mayo score of 4–6, an endoscopic subscore ≥2 and a rectal bleeding subscore ≥1, and no prior bio/JAKi exposure. Methods GLADIATOR (NCT04607837) was a multicentre, phase 2, double-blind trial. Adult patients with mildly to moderately active UC were randomised 2:1 to etrasimod 2 mg QD or placebo for 52 weeks in a treat-through study design. 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 was assessed at Week 52. Results In total, 104 and 46 patients who were bio/JAKi-naïve received etrasimod and placebo, respectively. Baseline characteristics were generally similar across treatment arms (Table). At Week 12, significantly greater proportions of patients receiving etrasimod versus placebo achieved clinical remission (30.8% vs 10.9%; p = 0.003), endoscopic improvement (45.2% vs 19.6%; p = 0.001), symptomatic remission (38.5% vs 21.7%; p = 0.041) and EIHR (30.8% vs 15.2%; p = 0.032). The same was observed for sustained clinical remission at Week 52 (19.2% vs 4.3%; p = 0.003; Figure). Numerically greater proportions of patients receiving etrasimod versus placebo achieved all other endpoints at Week 52. Safety in GLADIATOR was consistent with the known safety profile of etrasimod. Conclusion Etrasimod demonstrated efficacy in patients with mildly to moderately active UC and no prior bio/JAKi exposure, supporting the favourable benefit–risk profile and early use in the UC treatment algorithm. 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: Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson. 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. Rubin, David T.: Consultancy/Advisory fees from: AbbVie, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celltrion, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly & Co., Foresee, Genentech (Roche) Inc., Image Analysis Group, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer Inc, Sanofi, Takeda Pharmaceuticals, Throne, and Vedanta Grant support from: GastroIntestinal Research Foundation, Helmsley Charitable Trust, and Takeda Board of Trustees for: Cornerstones Health, Inc. 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.