Subgroup Analysis of Ozanimod Efficacy by Prior Biologic Exposure in Japanese Patients With Ulcerative Colitis from the Phase 2/3 J-True North Study

Background:
Ozanimod, a selective sphingosine 1-phosphate receptor modulator, is approved for the treatment of moderately to severely active ulcerative colitis (UC) in the United States and European Union and is being studied for use in Japan.
Methods:
J-True North was a multicenter, randomized, double-blind, placebo-controlled, phase 2/3 study that evaluated the efficacy and safety of ozanimod in Japanese patients with moderately to severely active UC. In a treat-through design, J-True North patients received once-daily placebo or ozanimod (0.46 mg or 0.92 mg) in the 12-week induction period, and clinical responders at Week (W) 12 continued each treatment in the following 40-week maintenance period. This subgroup analysis evaluated rates of clinical response and remission at W12 and W52 in patients with or without prior biologic exposure. Clinical response was defined as a reduction from baseline in the complete Mayo score of ≥3 points and ≥30%, and a reduction from baseline in the rectal bleeding subscore (RBS) of ≥1 point or an absolute RBS of ≤1 point. Clinical remission was defined as RBS = 0 and stool frequency subscore (SFS) ≤1 (and a decrease of ≥1 point from the baseline SFS) and Mayo endoscopy subscore ≤1.
Results:
A total of 198 patients were included in this analysis (biologic-naive, N=156; biologic-experienced, N=42). A higher proportion of biologic-naive patients receiving ozanimod 0.92 mg achieved a clinical response at W12 and W52 compared with those receiving placebo (W12: 63.5% [33/52] vs 35.3% [18/51]; W52: 51.9% [27/52] vs 17.6% [9/51]). In biologic-experienced patients, more patients achieved clinical response with ozanimod 0.92 mg compared with placebo at W12 and W52 (W12: 53.8% [7/13] vs 21.4% [3/14]; W52: 38.5% [5/13] vs 14.3% [2/14]). More biologic-naive patients achieved clinical remission at W12 and W52 with ozanimod 0.92 mg compared with placebo (W12: 26.9% [14/52] vs 0% [0/51]; W52: 32.7% [17/52] vs 7.8% [4/51 ]). In patients who were biologic-experienced, the clinical remission rate at W12 and W52 was 15.4% (2/13) in the ozanimod group; at W12 and W52, the clinical remission rate was 7.1% (1/14) in the placebo group.
Conclusions:
Although this analysis was limited by small sample sizes, the efficacy of ozanimod was shown in Japanese patients with active UC regardless of prior biologic exposure.