Efficacy and Durability of Ozanimod by Baseline Endoscopic Disease Activity in Advanced Therapy-Naive Ulcerative Colitis Patients Suboptimally Controlled on Conventional Therapies

Introduction: Many patients (pts) with ulcerative colitis (UC) initiate conventional therapies (CTs; 5-aminosalicylate, corticosteroids, and thiopurines) but are hesitant to progress to biologic advanced therapies (ATs). Ozanimod (OZA), an oral small molecule AT, is approved in multiple countries for the treatment of moderately to severely active UC. Methods: This analysis of the phase 3 True North (TN) study and subsequent open-label extension (OLE) explored OZA efficacy and durability in AT-naive UC pts inadequately controlled on CTs at TN baseline. AT-naive pts were grouped by baseline endoscopic disease activity as moderate (Mayo endoscopy subscore [MES]=2) or severe (MES=3). In the 10-wk induction period (IP), pts in Cohort 1 (C1) were randomized to OZA 0.92 mg or placebo (PBO) or received open-label OZA in Cohort 2. OZA clinical responders at Week (W) 10 were rerandomized to OZA (OZA/OZA) or PBO (OZA/PBO) during the maintenance period (MP) through W52. W52 OZA/OZA clinical responders continued in the OLE. Clinical and mucosal efficacy endpoints were evaluated at IP W10, MP W52, OLE W46, and OLE W94. Results: A total of 296 moderate and 320 severe pts were included in this analysis. Baseline pt characteristics were similar between groups, but with slightly higher prior immunomodulator use in severe vs moderate pts (Table 1). OZA was more effective than PBO in achieving all efficacy endpoints at W10; treatment differences (OZA [C1] vs PBO) were greater in moderate vs severe pts for all endpoints (Figure 1A). More OZA/OZA vs OZA/PBO pts achieved clinical and mucosal efficacy at W52; treatment differences (OZA/OZA vs OZA/PBO) were slightly greater in moderate vs severe pts for all endpoints except endoscopic improvement (Figure 1B). Eighty-two W52 OZA/OZA responders entered the OLE (moderate, n=45; severe, n=37); efficacy rates at OLE W46 were similar in moderate and severe pts and were maintained through OLE W94 in the observed case analysis (Figure 1C). Overall, the data followed similar patterns in the nonresponder imputation analyses across endpoints. Conclusion: OZA was efficacious and durable in AT-naive UC pts whose disease was inadequately controlled on CTs. Pts with moderate disease benefitted more from OZA during the first year of therapy, especially during induction, but long-term durability of OZA for up to 3 years was similar in moderate and severe OZA clinical responders. OZA may be an appropriate oral AT option for achieving and sustaining long-term benefit in AT-naive UC pts.Figure 1.: Efficacy during TN IP, TN MP, and TN OLE in AT-naive pts by baseline endoscopic disease activity. Table 1. - Demographic and clinical characteristics at baseline in the IP of AT-naive pts by baseline endoscopic disease activity AT-naive moderatea AT-naive severeb PBO (C1) n=64 OZA (C1) n=138 OZA (C2) n=94 PBO (C1) n=73 OZA (C1) n=149 OZA (C2) n=98 Age, y, mean (SD) 42.6 (13.6) 41.9 (13.2) 42.9 (14.9) 42.7 (14.1) 41.8 (13.4) 45.1 (12.8) Males, n (%) 38 (59.4) 78 (56.5) 54 (57.4) 52 (71.2) 86 (57.7) 64 (65.3) Years since UC diagnosis, mean (SD) 6.3 (7.0) 5.5 (5.9) 6.0 (7.4) 5.9 (7.4) 5.9 (6.0) 8.0 (8.5) Extensive disease, n (%) 16 (25.0) 41 (29.7) 21 (22.3) 31 (42.5) 52 (34.9) 32 (32.7) CS use at screening, n (%) 18 (28.1) 23 (16.7) 20 (21.3) 21 (28.8) 40 (26.8) 24 (24.5) Prior 5-ASA use, n (%) 62 (96.9) 135 (97.8) 94 (100.0) 72 (98.6) 146 (98.0) 98 (100.0) Prior CS use, n (%) 42 (65.6) 92 (66.7) 57 (60.6) 47 (64.4) 96 (64.4) 66 (67.3) Prior IMM use, n (%) 15 (23.4) 27 (19.6) 12 (12.8) 18 (24.7) 50 (33.6) 22 (22.4) aModerate pts had MES=2 at baseline.bSevere pts had MES=3 at baseline.5-ASA, 5-aminosalicylate; CS, corticosteroid; IMM, immunomodulator.