Document resource
Introduction Etrasimod is a novel oral selective S1PR modulator recommended for induction and maintenance of remission in moderate-to-severe ulcerative colitis (UC). Safety considerations include potential cardiac conduction abnormalities, which warrant baseline electrocardiography (ECG), as well as recommended ophthalmologic assessment with optical coherence tomography (OCT). Real-world evidence of its safety and effectiveness remains limited.Methods A retrospective observational cohort was assembled across six tertiary centres. All UC patients who received etrasimod at each site were included. Demographic data, cardiovascular and ophthalmologic evaluations, adverse events, treatment persistence, disease activity indices (SCCAI, UCEIS) and faecal calprotectin at baseline, 3 and 6 months were collected.Results 193 patients were analysed, with a median age of 38 years (IQR 29–49.5). Disease extent included 19.7% proctitis, 44.6% left-sided colitis, 31.6% extensive UC, 1.0% IBD-U and 3.1% unknown. 123 (63.7%) were advanced therapy (AT)-naïve. Of those exposed to AT, the median (range) number of ATs was 2 (0-9). Baseline ECG was performed in 97.4% with six (3.1%) patients requiring first dose ambulatory cardiac monitoring. OCT was completed in 115/165 (69.7%) patients within three months of starting therapy.Adverse events were reported in 30 (15.5%) patients: headache (23.3%), lymphopaenia (16.6%, lymphocyte count <0.5 × 10^9/L), blurred vision (13.3%), and dizziness or lightheadedness (13.3%). One case of bradycardia (HR <45bpm) and one case of first-degree atrioventricular block were reported. No major ophthalmologic complications were observed. Treatment persistence at the time of analysis was 63.2% with a median follow-up of 7 months (IQR 3-10.8). The main reasons for treatment discontinuation were lack of clinical response (47 patients, 24.4%) and adverse events (12 patients, 6.2%).165 (86%) patients completed 12 weeks of treatment at which time significant improvements were observed in disease activity and biomarkers; SCCAI scores (n=83) decreased from 4.6 to 3.1 (p < 0.0001), faecal calprotectin (n=50) fell from 942 µg/g to 478 µg/g (p = 0.002), and UCEIS (n = 50) from 4.1 to 2.8 (p < 0.0001). 119 (61.6%) patients had ≥6 months of follow-up.Multivariable logistic regression analysis identified prior exposure to a greater number of AT as significantly associated with lower treatment persistence (OR 0.51; 95% CI 0.3–0.8; p = 0.016). No other factors showed a significant association with persistence.Conclusions This real-world study demonstrated a safety and efficacy profile consistent with data from the registration studies of etrasimod in UC, supporting its role in clinical practice. Ongoing, well curated real-world datasets will enhance our understanding of this novel mechanism of action further.