C0387 - Ozanimod Is an Effective Oral Treatment for Patients With Ulcerative Colitis Regardless of Moderate or Severe Endoscopic Disease Activity at Baseline: A Post Hoc Analysis of the Phase 3 True North Study

Introduction: Ozanimod (OZA), an oral S1P receptor modulator, is effective and well tolerated in the treatment of moderate to severely active ulcerative colitis (UC). OZA is approved in this patient (pt) population based on results of the phase 3, randomized, double-blind, placebo (PBO)-controlled True North (TN) study (NCT02435992). Disease activity may influence treatment outcomes. Consequently, this post hoc analysis of TN explored the effect of baseline endoscopic disease activity on OZA efficacy.

Methods: In TN, pts were randomized to oral OZA 0.92 mg once daily or PBO (Cohort 1) or to open-label OZA (Cohort 2) for a 10-week induction period (IP). OZA clinical responders were rerandomized at Week 10 to OZA or PBO for a 42-week maintenance period (MP). Efficacy was assessed at Weeks 10 and 52, subgrouped by endoscopic disease activity at baseline (“moderate,” Mayo endoscopic score [MES]=2, or “severe” [MES=3]).

Results: Baseline demographics were similar in pts with moderate or severe disease. OZA was more effective than PBO regardless of baseline endoscopic severity at Weeks 10 and 52 for all evaluated endpoints (Table). Treatment effects at Week 10 (OZA vs PBO; Cochran-Mantel-Haenszel [CMH] test, stratified by corticosteroid [CS] use at screening and prior anti-tumor necrosis factor) were similar in pts with moderate or severe disease: Clinical Remission (CRem; odds ratio [OR] 3.4 [95% CI 1.6-7.2]; P=.0007; and 4.1 [95% CI 1.2-14.1]; P=.0198), Clinical Response (CRes; 2.6 [1.5-4.4]; P=.0006; and 2.7 [1.6-4.4]; P=.0001), Endoscopic Improvement (EI; 2.6 [1.5-4.7]; P< .001; and 3.7 [1.5-9.2]; P=.003), and Mucosal Healing (MH; 3.1 [1.3-7.4]; P=.0066; and 8.0 [1.01-63.2]; P=.0221), respectively (Figure). Tx effects at Week 52 (OZA-OZA vs OZA-PBO; CMH test, stratified by Week 10 CRem and CS use at Week 10) were similar in pts with moderate or severe disease: CRem (OR 3.1 [95% CI 1.7-5.7]; P=.0003; and 2.5 [95% CI 1.3-4.7]; P=.0038), CRes (2.6 [1.5-4.6]; P=.0007; and 2.2 [1.3-3.7]; P=.0043), EI (2.5 [1.4-4.4]; P=.002; and 2.7 [1.5-4.9]; P< .001), CS-free remission (2.7 [1.4-5.1]; P=.0027; and 2.8 [1.4-5.7]; P=.0032), and MH (3.2 [1.6-6.1]; P=.0005; and 2.4 [1.2-4.9]; P=.0182), respectively (Figure).




Discussion: This post hoc analysis of the phase 3 TN study shows that OZA is effective at achieving clinical endpoints at Weeks 10 and 52 in pts with BL moderate or severe endoscopic disease activity. OZA is efficacious in UC pts regardless of BL endoscopic disease activity.