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OP09 Histological remission and mucosal healing in a randomised, placebo-controlled, Phase 2 study of etrasimod in patients with moderately to severely active ulcerative colitis

L. Peyrin-Biroulet*1, J. Panés2, M. Chiorean3, J. Zhang4, S. Vermeire5, V. Jairath6, A. Yarur7, C. Cabell4, S. Naik4, W. J. Sandborn8

1University Hospital of Nancy, Vandœuvre-lès-Nancy, France, 2Hospital Clinic of Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, 3Virginia Mason Medical Center, Seattle, USA, 4Arena Pharmaceuticals, Inc., San Diego, USA, 5University Hospitals Leuven, Leuven, Flanders, Belgium, 6Western University, London, Ontario, Canada, 7Medical College of Wisconsin, Milwaukee, USA, 8University of California San Diego, La Jolla, USA

Background

Etrasimod (APD334), an oral, selective sphingosine-1-phosphate receptor modulator, was evaluated in the randomised, double-blind, placebo-controlled, parallel-group, Phase 2 OASIS study (ClinicalTrials.gov identifier: NCT02447302) in patients with moderately to severely active ulcerative colitis (UC). Etrasimod demonstrated dose-dependent improvements in clinical response, clinical remission, and endoscopic appearance and decreased circulating lymphocytes. Here, we describe histological remission and mucosal healing results at Week 12.

Methods

Patients were randomised to receive once-daily etrasimod 1 mg (n = 52) or 2 mg (n = 50), with no dose titration, or placebo (n = 54). At baseline and Week 12, endoscopic severity was assessed by sigmoidoscopy with central readings using the Mayo endoscopic subscore. Biopsies were taken, and histology results were scored by a blinded central pathologist using the Geboes index. Prespecified endpoint definitions were endoscopic improvement (Mayo endoscopic subscore of 0 or 1); histological improvement (Geboes score <3.1); and histological remission (Geboes score <2.0). Mucosal healing (a post hoc analysis) was defined as both endoscopic improvement and histological remission. Differences between groups were estimated using the Mantel–Haenszel analysis adjusted for current corticosteroid use at baseline and prior anti-tumour necrosis factor α use.

Results

Of 156 patients randomised, 90% completed the study. Etrasimod 2 mg, compared with placebo, resulted in significantly more patients who achieved endoscopic improvement (43.2% vs. 16.3%, respectively; p = 0.003), histological improvement (31.7% vs. 10.2%; p = 0.006), and histological remission (19.5% vs. 6.1%; p = 0.027) at Week 12 (Table). Mucosal healing was seen in 19.5% and 4.1% of patients treated with etrasimod 2 mg and placebo, respectively (p = 0.010). More patients receiving etrasimod 1 mg also achieved each endpoint compared with placebo; however, results did not reach statistical significance.

Conclusion

Etrasimod 2 mg induced significantly higher rates of endoscopic improvement, histological improvement and remission, and mucosal healing in patients with moderately to severely active UC when compared with placebo. Mucosal healing may prove to be an achievable and objective measure of drug efficacy in UC induction studies.

Abstract OP09 – Table. Endoscopic, histological, mucosal measures at Week 12.