Real-world effectiveness and safety of etrasimod in ulcerative colitis: Interim analysis of the effect-UC study

Abstract

Background: Etrasimod is an oral, once-daily, selective sphingosine 1phosphate (S1P) receptor modulator for the treatment of ulcerative colitis (UC). The positive benefit-risk profile of etrasimod was demonstrated in the phase 3 ELEVATE UC clinical programme and ENLIGHT UC trial. Here we report an interim analysis of the first prospective real-world data for etrasimod up to 24 weeks of treatment. Method(s): EFFECT-UC (NCT06294925) is an ongoing, prospective, multinational, noninterventional study enrolling adults with moderately to severely active UC starting etrasimod in routine care in the United Kingdom (UK), Germany and Canada. The coprimary endpoints are symptomatic remission at Week 12 and Week 52. Secondary endpoints include patient-reported outcome (PRO) 2 response at Week 12 and Week 52. Exploratory endpoints include bowel urgency (BU) assessed using an 11-point numerical rating scale (NRS). All PROs are collected at 2, 6, 12, 24, 36 and 52 weeks of treatment. In this interim analysis, descriptive analyses are presented as observed up to Week 24 with no imputation for missing data. Result(s): As of 16 June 2025, 121 patients (UK n = 59; Germany n = 57; Canada n = 5) had received etrasimod and were included in the full analysis set (mean age 40.2 years; 40.5% female; mean duration of UC 7.8 years; 60.3% biologic/Janus kinase inhibitor naive). Mean baseline PROs were 1.6 for stool frequency subscore (SFS), 0.9 for rectal bleeding subscore (RBS), 2.5 for PRO2 and 5.4 for BU NRS (Table). Of patients with available data at Week 12 (N = 63), 31 (49.2%) were in symptomatic remission and 49 (77.8%) had PRO2 response (Figure). Improvements in SFS, RBS and BU were observed from Week 2 (Figure). In the safety analysis set (N = 122), 57 (46.7%) patients reported treatment-emergent adverse events (AEs). Five patients (4.1%) reported six serious AEs (UC flare, proctocolectomy, syncope, two concurrent gastrointestinal infections and one event currently uncoded); all were resolved/resolving and deemed unrelated to study drug by the treating physician. Conclusion(s): In this first report of real-world data from the ongoing EFFECTUC study, etrasimod demonstrated clinically meaningful effectiveness for up to 24 weeks of treatment in patients with moderately to severely active UC. No new safety signals were identified. These findings and future analyses provide important real-world evidence supporting the use of etrasimod in routine clinical practice.