Long-Term Ozanimod Therapy in Patients With Moderately Active Ulcerative Colitis After Failure of 5-Aminosalicylic Acid.

Background: We evaluated the efficacy and safety of ozanimod after 5-aminosalicylic acid (5-ASA) failure in advanced therapy (AT)-naive patients with moderate ulcerative colitis (UC) in True North and its open-label extension (OLE).

Methods: True North was a randomized, 52-week, phase 3 trial with an optional OLE. Efficacy was assessed in True North and the OLE; safety was assessed through OLE week 190.

Results: Overall, 203 AT-naive True North patients had moderate UC (Mayo endoscopic subscore of 2 + modified Mayo score of 4-6 + rectal bleeding subscore ≥1). Of these, 139 were also immunomodulator-naive and not receiving corticosteroids (5-ASA-exposed only) at baseline. Patients with moderate UC receiving ozanimod vs placebo achieved greater efficacy rates for all week 10 and week 52 outcomes, regardless of prior immunomodulator/corticosteroid use (eg, week 10 clinical remission: AT-naive = 36.8% vs 10.6%; 5-ASA-exposed only = 37.9% vs 17.2%). Higher symptomatic response rates were achieved by week 2 with ozanimod in AT-naive patients with moderate UC vs the overall AT-naive population (50.5% vs 38.7%); similar trends were observed in patients exposed only to 5-ASA. Efficacy was maintained through OLE week 190 in patients who entered OLE as True North week 52 ozanimod clinical responders. Of those entering OLE as True North week 10 ozanimod clinical nonresponders, 69.0% of AT-naive patients and 68.4% of patients exposed only to 5-ASA achieved symptomatic response by week 5. No new safety signals emerged.

Conclusions: Ozanimod was safe, effective, and durable up to ∼5 years in AT-naive patients with moderate UC who failed conventional therapy. ClinicalTrials.gov: NCT02435992, NCT02531126.