Real-World Efficacy and Safety of Ozanimod in US Patients With Moderately to Severely Active Ulcerative Colitis: Initial Results from POLARIS, an Ongoing Phase 4 Open-Label Study

Background:
Ozanimod (OZA) is an oral, selective sphingosine 1-phosphate receptor 1 and 5 modulator approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults. This study evaluates the efficacy and safety of OZA in real-world clinical practice.
Methods:
POLARIS is an ongoing, prospective, open-label, phase 4 study of US patients (pts) with moderately to severely active UC from real-world clinical practices. Pts are enrolled in 2 cohorts: advanced therapy–naive (AT; ie, naive to thiopurines and any biologics) (Cohort [C] 1) or AT-exposed (ie, failed 1 prior mechanism of action [MOA] of biologics) (C2). The primary endpoint is clinical response at Week (W) 12 for C1 and W26 for C2. The W26 assessment for C2 was chosen based on the historically delayed response to next-line therapies in biologic-experienced patients. Secondary endpoints include clinical remission, endoscopic response, endoscopic improvement, histological improvement, and Inflammatory Bowel Disease Questionnaire (IBDQ) response and remission at W12 (C1) and W26 (C2); endoscopic and histologic remission were also assessed at W26 (C2). Safety assessments include treatment-emergent adverse events (TEAEs).
Results:
Among 65 pts included in this analysis (C1, n=51; C2, n=14), mean age was 43.2 years, mean body mass index was 27.7, 78.5% were white, and 15.4% were Hispanic or Latino. Baseline demographics and disease characteristics were generally similar across cohorts, but pts in C2 vs C1 had more males, longer disease duration, and higher proportion of severe UC. Corticosteroid use at screening was reported in 15 (29.4%) pts in C1 and 4 (28.6%) pts in C2. In C2, 50% had received prior anti–tumor necrosis factor and 14.3% had received prior vedolizumab. The primary endpoint of clinical response was achieved by 70.6% at W12 in C1 and 57.1% at W26 in C2. Clinical remission was achieved by 31.4% at W12 in C1 and 42.9% at W26 in C2. All other secondary endpoints were also achieved by a large proportion of pts. TEAEs were reported in 46.2% of the overall population, with no drug-related TEAEs leading to discontinuation of study treatment and few serious TEAEs (3.1%). No new signals regarding adverse events of special interest (ie, opportunistic infections, cardiovascular events, hepatic events, macular edema, and malignancies) were identified.
Conclusions:
In real-world clinical practice, pts achieved high efficacy rates with OZA at W12 for AT-naive and at W26 for AT-exposed pts, indicating benefit after conventional therapies or after failing 1 biologic MOA. Similar trends were observed with IBDQ endpoints, thus demonstrating early composite evidence of OZA impact on quality of life. No new safety signals were identified.