P1030Effectiveness and Safety of Etrasimod in Moderate to Severe Ulcerative Colitis: A Real-World Multicenter Study

Abstract Background Etrasimod is an oral, selective sphingosine-1-phosphate (S1P) receptor modulator that regulates lymphocyte trafficking and has shown efficacy and a favourable safety profile in phase 2–3 trials in ulcerative colitis (UC). Real-world evidence, however, remains limited. This study aimed to evaluate the effectiveness and safety of etrasimod in routine practice in patients with moderately to severely active UC. Methods This multicentre, retrospective study included patients aged ≥16 years with active UC treated with etrasimod 2 mg once daily across eleven Italian IBD centres, with ≥12 weeks of follow-up. The primary endpoint was week-12 clinical remission, defined as RB = 0 and SF = 0–1 with a ≥ 1-point decrease from baseline. Secondary endpoints included corticosteroid-free and sustained clinical remission (weeks 12 and 24), endoscopic improvement (MES ≤1), bowel-urgency remission (NRS 4/10), intestinal ultrasound (IUS) remission (MUC ≤6.2), and normalization of fecal calprotectin (FC) (≤150 µg/mg) and C-reactive-protein (CRP) (≤5 mg/L). Results Thirty-nine patients completed week-12 follow-up (51.3% male). Most patients presented with a baseline MES of 3 (57.9%) and had extensive colitis (59.0%). Over half (53.8%) had prior exposure to advanced therapies, including 28.2% with 2 such agents, while 46.2% were treatment-naïve. Clinical remission was achieved in 48.7% (19/39) at week 12 and 69.2% (9/13) at week 24, with 46.1% (6/13) sustaining remission. Week-12 secondary outcomes included: steroid-free remission 41.0% (16/39), endoscopic improvement 23.5% (4/17), bowel-urgency remission 59.0% (23/39), IUS remission 70.0% (7/10), FC normalization 36.0% (9/25), and CRP normalization 71.4% (20/28). Adverse events through week 12 were lymphocytopenia (23.1%), AST/ALT elevations (23.1%), influenza-like symptoms (7.7%), sinus bradycardia (2.6%), and Mobitz I ventricular-atrium block (2.6%), neither requiring discontinuation. No macular oedema, opportunistic infections, malignancies, or UC-related surgeries occurred. Treatment discontinuation reached 15.4% (6/39) by week 12. No baseline characteristic independently predicted week-12 remission, though trends suggested lower odds with extensive disease and prior exposure to 2 advanced therapies, and higher odds in biologic-naïve patients. Conclusion This is the first real-world multicentre study confirming the effectiveness and reassuring safety profile of etrasimod at week 12 in moderately to severely active UC. Further studies with larger sample size and longer follow-up are warranted. Conflict of interest: Dr. D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Centanni, Lucia: No conflict of interest Miranda, Agnese: No conflict of interest Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar Gabbiadini, Roberto: No conflict of interest Mastronardi, Mauro: none Massironi, Sara: None to declare Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Giorgio, Valentina: No conflict of interest Annunziata, Maria Laura: No conflict of interest Quadarella, Alessandro: I have no conflict of interest. Gravina, Antonietta Gerarda: Gravina AG has conducted training activities e.g. educational continuing medical activities (ECM), preceptorship for Pfizer, Galapagos Biopharma, and AbbVie. Saibeni, Simone: Consultancy, lecture fees, and advisory board for AbbVie, Alfasigma, Arena, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Johnson & Johnson, MSD, Pfizer, and Takeda. Allocca, Mariangela: Personal Fees: consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, Pfizer, Ferring, Galapagos, Sandoz, Lilly and Alfasigma Furfaro, Federica: Grant: IG-IBD Personal Fees: Pfizer, Biogen, J&J, Abbvie, Amgen, Janssen Zilli, Alessandra: Personal Fees: Speaking and consulting fees from Tillotts, Galapagos, Abbvie, Takeda, Janssen, Alfasigma, Sandoz, Lilly, Pfizer Massimino, Luca: No conflict of interest Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda