Document resource
Introduction 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. 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 1). 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%).Conclusions 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.Abstract P225 Table 1Safety data from the etrasimod UC clinical programme