P0802Etrasimod Real-World Experience in Ulcerative Colitis: A multicentre cohort study

Abstract Background Etrasimod is a novel oral selective sphingosine 1-phosphate receptor (S1PR) modulator recommended for induction and maintenance of remission in moderate-to-severe ulcerative colitis (UC). Safety considerations include potential cardiac conduction abnormalities warranting baseline electrocardiography (ECG). In addition, ophthalmologic assessment with optical coherence tomography (OCT) is recommended within 3 months of starting treatment. Real-world evidence of its safety and effectiveness remains limited. Methods A retrospective observational study was conducted across six tertiary centers. All patients with UC treated with etrasimod at each centre were included. Demographic data, cardiovascular and ophthalmologic assessments, adverse events, treatment persistence, disease activity indices (SCCAI, UCEIS) and faecal calprotectin at baseline, 3 and 6 months were collected. Results 193 patients were included, with a median age of 38 years (IQR 29–49.5). 19.7% of patients had proctitis, 44.6% left-sided disease, 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 × 109/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. Conclusion This real-world study of etrasimod 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. Reference: Sandborn WJ, Vermeire S, PeyrinBiroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, doubleblind, placebocontrolled, phase 3 studies. Lancet. 2023;401(10383):11591171. doi:10.1016/S01406736(23)000612 Conflict of interest: Mx. Vayreda, Eva: No conflict of interest Vasconcellos S. Reis, Paola: No conflict of interest Matini, Lawrence: Speaker fees: AbbVie, Galapagos, Bristol Myers Squibb Punj Sharda, Anita: I declare that I have no conflicts of interest. Dunbar, Grace: No conflicts Hall, Richard: Speaker fees - Takeda Lopezosa Estepa, Teresa: No conflict of interest Williams, Stephanie: No conflict of interest Islam, Samiha: No conflict of interest Javed, Anum: No conflict of interest Patel, Kamal Vijaykant: Received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, Dr. Falk Pharma, PredictImmune, Pfizer, and Ferring and has received advisory board fees from Abbvie, Galapagos, Pfizer, and Janssen. He has also received a grant from AbbVie to support research. Honap, Sailish: Sailish Honap has served as a speaker, consultant, advisory board member, and/or received travel grants from AbbVie, AlfaSigma, Banook Group, Ferring, Johnson & Johnson, Lilly, Pharmacosmos, Pfizer, and Takeda. Mehta, Shameer: Personal fees: Pfizer, Takeda, Johnson & Johnson Walsh, Alissa: Grant: Alfasigma, Helmsley Trust, Johnson & Johnson, Pfizer, Takeda Personal Fees: AbbVie, Alfasigma, Bristol Meyers Squibb, Dr Falk, Ferring, Johnson & Johnson, Lilly, Pfizer, Takeda, Tillotts Alexander, James: James has received speaker fees from Pfizer, Abbvie, Takeda and Janssen. He has received travel grants and support to attend meetings from Lilly, Tillotts Pharma, Takeda and Celltrion. Irving, Peter Miles: Grant: MSD, Pfizer, Takeda, Celltrion, Galapagos Personal Fees: AbbVie, Arena, BMS, Boomerang Medical, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Sapphire Medical, Sandoz, Shire, Takeda, Tillotts, Topivert, VH2, Vifor Pharma, Warner Chilcott