E0343 - Ozanimod Is an Effective Oral Treatment for Patients With Ulcerative Colitis Regardless of Baseline Endoscopic Disease Distribution: A Post Hoc Analysis of the Phase 3 True North Study

Introduction: Ozanimod (OZA), an oral S1P₁ and S1P₅ receptor modulator, is effective and well tolerated in the treatment of moderate to severely active ulcerative colitis (UC) patients (pts). OZA is approved in this pt population based on results of the phase 3, randomized, double-blind, placebo (PBO)-controlled True North (TN; NCT02435992) study. Disease extent may influence treatment outcomes, including clinical symptoms and colectomy risk. Consequently, this post hoc analysis of TN explored the effect of baseline disease extent on OZA efficacy.

Methods: In TN, pts were randomized to OZA 0.92 mg once daily or PBO (Cohort 1) or to open-label OZA (Cohort 2) for a 10-wk induction period (IP). OZA clinical responders were rerandomized at Week (W) 10 to OZA or PBO for a 42-wk maintenance period (MP). Efficacy was assessed at W10 and W52, subgrouped by disease extent at baseline (BL; left-sided [LS] or extensive [EXT] colitis).

Results: BL demographics and disease characteristics were similar in LS and EXT UC pts. OZA was more effective than PBO in pts with LS and EXT disease distribution at W10 and W52 for all clinical outcomes (Table). At W52, corticosteroid (CS)-free remission was achieved in 30.9% and 17.2% OZA-OZA and OZA-PBO LS UC pts, and in 33.3% and 15.7% OZA-OZA and OZA-PBO EXT UC pts. Treatment effects at W10 (OZA vs PBO, Cochran-Mantel-Haenszel [CMH] test, stratified by CS use at screening and prior anti-TNF) were generally similar in LS and EXT UC pts: Clinical Remission (CRem; odds ratio [OR] 4.1 [95% CI 1.9-9.0]; P=.0001 & 2.8 [1.02-7.6]; P=.0387), Clinical Response (CRes; 3.0 [1.9-4.7]; P=.0001 & 2.3 [1.3-4.2]; P=.0066), Endoscopic Improvement (EI; 2.9 [1.6-5.0]; P< .001 & 2.5 [1.1-5.7]; P=.024), and Mucosal Healing (MH; 5.4 [1.9-15.4]; P=.0006 & 2.1 [0.7-6.5]; P=.1675), respectively (Fig). Treatment effects at W52 (OZA-OZA vs OZA-PBO, CMH test, stratified by CRem status and CS use at W10) were generally similar for LS and EXT UC pts: CRem (OR 2.7 [95% CI 1.6-4.5]; P=.0003 & 2.8 [1.3-6.2]; P=.0084), CRes (2.4 [1.5-3.8]; P=.0003 & 2.0 [1.01-3.9]; P=.0468), EI (2.4 [1.5-3.9]; P< .001 & 2.8 [1.3-6.1]; P=.007), CS-free remission (2.3 [1.3-4.0]; P=.0040 & 3.4 [1.5-8.0]; P=.0035), and MH (2.4 [1.4-4.2]; P=.0022 & 4.0 [1.6-10.6]; P=.0033), respectively (Fig).

Discussion: This post hoc analysis shows that OZA is effective at achieving all clinical endpoints assessed at W10 and W52 in pts with LS and EXT disease distribution at BL. OZA is efficacious in UC pts regardless of disease extent.