S14 Duration of Response After Ozanimod Withdrawal: Phase 3 True North Study Results

Abstract

Background: The phase 3 True North (TN) randomized trial demonstrated efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis (UC). Temporary discontinuation of UC treatment can occur in clinical practice. Understanding the duration of response after treatment discontinuation can assist in clinical decision making. This analysis examined time to disease relapse in patients who discontinued ozanimod and switched to placebo in the TN maintenance period (MP). Methods: In TN, patients were randomized to once-daily oral ozanimod 0.92 mg or placebo or to open-label ozanimod during a 10-week induction period (IP). Patients with clinical response to ozanimod at Week 10 were rerandomized to ozanimod (continuous ozanimod) or placebo (ozanimod/placebo) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points versus Week 10 with absolute PMS ≥4, endoscopic subscore ≥2, and exclusion of other causes of increased disease activity unrelated to UC. A subanalysis compared outcomes in continuous ozanimod and ozanimod/placebo patients who entered the MP after achieving clinical remission or clinical response only (excluding patients in clinical remission) at Week 10. Results: In the TN MP, 230 patients continued ozanimod (clinical remission, n = 82; clinical response only, n = 148) and 227 patients switched to placebo (clinical remission, n = 79; clinical response only, n = 148). Baseline characteristics were generally similar between groups, except the group achieving clinical remission had less severe disease at baseline and fewer patients had a history of other prior immunosuppressive medication use than the group achieving clinical response only. Endoscopic disease severity improved from baseline, with all patients in clinical remission and 15.5% in clinical response achieving an endoscopic score of 0 or 1 at Week 10 (ie, MP entry). In the overall MP population, differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of patients on continuous ozanimod were without relapse versus those who switched to placebo. Kaplan-Meier (KM) estimates of no relapse at MP Week 42 were 86.1% for continuous ozanimod and 62.6% for ozanimod/placebo groups. Additionally, patients in clinical remission at Week 10 had higher rates of nonrelapse during the MP versus those in clinical response only at MP entry. KM estimates of nonrelapse at MP Week 42 were 90.9% for patients on continuous ozanimod and 67.9% for patients in the ozanimod/placebo group who achieved clinical remission, and 83.4% and 59.7% in the continuous ozanimod and ozanimod/placebo groups with clinical response only, respectively. Conclusion(s): This analysis shows that ozanimod is effective at preventing disease relapse over 42 weeks of maintenance treatment in patients who achieved clinical response at Week 10. These data show that ozanimod maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.