P1044 - Efficacy of Etrasimod by Disease Duration: An Analysis of the Phase 3 ELEVATE UC Clinical Program

Edward L. Barnes, MD, MPH¹, Fernando Magro, MD, PhD², Hiroshi Nakase, MD, PhD³, Raymond K. K. Cross, MD, MS, FACG⁴, Shannon Chang, MD⁵, Faten Aberra, MD, MSCE⁶, Jesse Green, MD⁷, Laure Kouyoudjian, MD, MS⁷, Abhishek Bhattacharjee, PhD⁸, Maria Kudela, PhD⁹, Martina Goetsch, MD¹⁰, Geert R. D'Haens, MD, PhD¹¹
1Multidisciplinary Inflammatory Bowel Diseases Center, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, Chapel Hill, NC; 2CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-450, Porto, Portugal, Porto, Porto, Portugal; 3Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Hokkaido, Japan, Sapporo, Hokkaido, Japan; 4Division of Gastroenterology and Hepatology, Melissa L. Posner Institute for Digestive Health & Liver Disease at Mercy Medical Center, Baltimore, MD, USA, Baltimore, MD; 5New York University Langone Health, New York, NY, USA, New York, NY; 6Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, Philadelphia, PA; 7Pfizer Inc, Collegeville, PA, USA, Collegeville, PA; 8Pfizer Healthcare India Private Ltd, Chennai, India, Chennai, Tamil Nadu, India; 9Pfizer Inc, Cambridge, MA, USA, Cambridge, MA; 10Pfizer AG, Zürich, Switzerland, Zürich, Zurich, Switzerland; 11Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam, The Netherlands, Amsterdam, Noord-Holland, Netherlands

Introduction: Ulcerative colitis (UC) can lead to irreversible damage, highlighting the importance of early intervention. While disease duration impacts response to therapy in Crohn’s disease,^1,2 similar evidence in UC is lacking.³ Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active UC. We evaluated the efficacy of etrasimod 2 mg QD vs placebo within disease duration subgroups in the ELEVATE UC clinical program.

Methods: In this post hoc analysis of ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients were assigned by disease duration (calculated using the date of diagnosis) into three subgroups: ≤ 2 years, > 2 to ≤ 5 years, > 5 years. In each disease duration subgroup, treatment comparisons and 2-sided p values (reported without adjustment to multiple comparisons) were obtained using the Cochran–Mantel–Haenszel method for clinical remission, clinical response, symptomatic remission, endoscopic improvement, and endoscopic improvement-histologic remission at Week 12 and Week 52, and corticosteroid-free and sustained clinical remission at Week 52.

Results: Baseline characteristics were generally balanced within each subgroup; however, a higher proportion of patients in the ≤ 2 years subgroup were biologic/Janus kinase inhibitor-naïve vs the other two subgroups (Table 1). At Week 12 in all subgroups, greater proportions of patients receiving etrasimod vs placebo met criteria for all endpoints (p < 0.05; Table 2). At Week 52, greater proportions of patients receiving etrasimod vs placebo met criteria for all endpoints in the > 5 years subgroup (p < 0.05), and met criteria for most endpoints in the ≤ 2 years and > 2 to ≤ 5 years subgroups (Table 2).

Discussion: Etrasimod demonstrated significant induction and maintenance efficacy vs placebo in both symptomatic and endoscopic endpoints, irrespective of disease duration. These results highlight the efficacy of etrasimod for patients with shorter or longer duration of UC. Future analyses are needed to compare efficacy across disease duration subgroups and longer-term maintenance of response.

Refs:

1. Ungaro R et al. Aliment Pharmacol Ther 2020; 51: 831–842.
2. Noor NM et al. Lancet Gastroenterol Hepatol 2024; 9: 415–427.
3. Solitano V et al. J Clin Med 2020; 9: 2646.

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.




Disclosures:


Edward L. Barnes, MD, MPH¹, Fernando Magro, MD, PhD², Hiroshi Nakase, MD, PhD³, Raymond K. K. Cross, MD, MS, FACG⁴, Shannon Chang, MD⁵, Faten Aberra, MD, MSCE⁶, Jesse Green, MD⁷, Laure Kouyoudjian, MD, MS⁷, Abhishek Bhattacharjee, PhD⁸, Maria Kudela, PhD⁹, Martina Goetsch, MD¹⁰, Geert R. D'Haens, MD, PhD¹¹. P1044 - Efficacy of Etrasimod by Disease Duration: An Analysis of the Phase 3 ELEVATE UC Clinical Program, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.