Abstract Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of ulcerative colitis (UC). We report an updated cumulative safety analysis from the etrasimod UC clinical programme, reflecting a maximum exposure up to 5 years. Methods We included patients who received etrasimod 1 or 2 mg QD in phase 2 (OASIS; OASIS open-label extension OLE; dose-ranging study in Japan; GLADIATOR), phase 3 (ELEVATE UC 52, ELEVATE UC 12, ELEVATE UC 40 JAPAN) and ongoing ELEVATE UC OLE (data cutoff 20 Jun 2024) and ENLIGHT UC OLE (data snapshot 30 Aug 2022) studies (Figure). We analysed treatment-emergent adverse event (AE) frequency and exposure-adjusted incidence rates (IRs) per 100 patient-years (PY). Results In total, 1268 patients received ≥1 dose of etrasimod 1 or 2 mg QD (mean standard deviation (SD) exposure 88.8 (67.5) weeks, with a maximum exposure of 251.0 weeks; total exposure 2156.9 PY). At baseline, patients had a mean (SD) age of 41.1 (13.4) years, 74.8% were white, 41.7% were female and 72.2% of patients were biologic/Janus kinase inhibitor-naïve. After up to 5 years of exposure, 79.8% of patients experienced any AE, 12.4% had AEs that led to treatment discontinuation (most commonly due to worsening UC), and serious AEs occurred in 12.2%. Three patients (IR/100PY: 0.13) had AEs leading to death, all deemed unrelated to study treatment (Table). Serious infections were infrequent (IR/100PY: 1.56) and treatment discontinuation due to an infection was rare (IR/100 PY: 0.68). Incidence of Macular oedema remained low (IR/100 PY: 0.27); all events were nonserious and resolved/resolving. No Hypertension events (IR/100 PY: 2.24) were serious or led to treatment discontinuation. Bradycardia and Atrioventricular (AV) block events were rare (each IR/100PY: ≤0.73); most occurred on the first day of etrasimod treatment, and only one event was serious (asymptomatic AV block resolving on Day 2 without intervention). Malignancies were uncommon (0.5%; IR/100PY: 0.27) and five patients had NMSC events (0.4%). Conclusion In this integrated safety analysis, including nine clinical trials in patients with moderately to severely active UC with etrasimod treatment exposure for up to 5 years, etrasimod was well tolerated and continues to have a favourable and stable safety profile. 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.: 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. Regueiro, Miguel: Advisory Boards and Consultant for: AbbVie, ALFASIGMA, S.p.A., Allergan, Amgen, Bristol Meyer Squibb (BMS), Celgene, Genentech, Gilead, Janssen, Lilly, Miraca Labs, Pfizer, Prometheus, Salix, Seres, Takeda, TARGET Pharma Solutions, and UCB Unrestricted Educational Grants from: AbbVie, BMS, Celgene, Genentech, Gilead, Janssen, Pfizer, Takeda, and UCB Royalties from: Wolters Kluwer Health Other: CME Companies: CME Outfitters, Cornerstones, GI Health Foundation (GiHF), Imedex, MJH life sciences, and Remedy. Takeuchi, Ken: Consultancy/advisory fees: Thermo Fisher Diagnostics K.K. Grant/research support: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, EA Farma, IQUVIA, Janssen, Lilly, Pfizer, Shin-nippon biomedical laboratories, Ltd., Takeda. Lecture/speaker fees: AbbVie, Celltrion healthcare, EA Pharma, Janssen, Kissei, Kyorin, Mochida, Nippon Shinyaku, Pfizer Inc, Takeda, Tanabe-Mitsubishi, Zeria. Walsh, Alissa: Grant/Research support from: AbbVie, Alfasigma, Bristol Myers Squibb, Buhlmann, Eli-Lilly, Falk, Galapagos, Janssen, Pfizer Inc, Sandoz, Takeda, and Tillotts. Kotze, Paulo Gustavo: Consulting and speaker fees from: AbbVie, Janssen, Pfizer Inc., and Takeda Scientific grants from: Pfizer Inc and Takeda. Charabaty, Aline: Consultant/Advisory Board for: AbbVie, Eli Lilly, Janssen, Pfizer, Sanofi and Takeda. Caldera, Freddy: Consultancy fees: GSK, Janssen. Scientific grants: GSK, Janssen, Novavax, Takeda. Lazin, Krisztina: Employee: Pfizer AG. Shareholder: Pfizer Inc. Goetsch, Martina: Employee: Pfizer AG. Shareholder: Pfizer Inc. Zang, Chuanbo: Employee: Pfizer Inc. Shareholder: Pfizer Inc. Tsamos, Georgios: Employee of Pfizer. Ferreira Branquinho, Diogo: Employee: Pfizer Inc Shareholder: Pfizer Inc Segovia Medina, Michelle: Employee: 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.
Rubin et al. (Thu,) studied this question.