A0392 - Ozanimod Is an Efficacious Oral Therapy After 5-ASA Failure in Immunomodulator- and Biologic-Naive Patients With Ulcerative Colitis: Post Hoc Analysis From True North

Introduction: Oral 5-ASAs and corticosteroids (CSs) are often first-line treatment for UC, and pts who fail these agents typically advance to immunosuppressives or biologics. Ozanimod (OZA), an oral S1P receptor modulator, is approved in the United States and EU for treating adults with moderately to severely active ulcerative colitis (UC). This post hoc analysis from the phase 3 True North (TN) randomized controlled trial evaluated the efficacy of OZA at Week 10 (end of induction) in immunomodulator- and biologic-naive pts with moderate to severe UC who failed 5-ASA with or without concomitant CSs.

Methods: TN consisted of a 10-week induction period. Pts in Cohort (C) 1, stratified by CS use at screening, were randomized to OZA 0.92 mg (equivalent to OZA HCl 1 mg; n=429) or placebo (PBO; n=216) once daily in a double-blind manner; pts in C2 (n=367) received open-label (OL) daily OZA 0.92 mg. At enrollment, pts were required to be on stable doses of oral 5-ASA and/or CSs for ≥2 weeks and continued on the same dose throughout induction. Pts who received tofacitinib within 2 weeks of screening were excluded. This analysis focused on clinical remission, clinical response, endoscopic improvement, and mucosal healing efficacy outcomes in immunomodulator- and biologic-naive, 5-ASA–exposed pts.

Results: Of 464 pts treated with 5-ASA who were immunomodulator- and biologic-naive, with or without CSs, 205 received OZA and 105 received PBO in C1; 158 pts received OL OZA in C2. Baseline characteristics were similar between groups in C1. Compared with PBO at Week 10, a higher proportion of OZA-treated pts achieved clinical remission (23.4% v 8.9%), clinical response (53.7% v 30.7%), endoscopic improvement (35.6% v 14.9%), and mucosal healing (18.0% v 5.0%) (Figure 1A) in this subgroup. These results are consistent with previously published results of the overall study population,¹ which demonstrated that significantly greater proportions of pts who received OZA v PBO achieved clinical remission (18.4% v 6.0%), clinical response (47.8% v 25.9%), endoscopic improvement (27.3% v 11.6%), and mucosal healing (12.6% v 3.7%). All efficacy endpoints were achieved by a greater proportion of pts receiving OZA v PBO regardless of CS use at baseline (Figure 1B). Results were similar for OL OZA-treated pts in C2.

Discussion: OZA demonstrated efficacy at Week 10 in immunomodulator- and biologic-naive pts with UC who had failed 5-ASA, regardless of CS use at baseline.

1. Sandborn WJ et al. N Engl J Med 2021;385:1280-91.