S723 Duration of Response to Ozanimod After Treatment Withdrawal: Results From the Phase 3 True North Study

Abstract

Introduction: The phase 3 True North (TN) randomized trial demonstrated efficacy and safety of ozanimod (OZA) in patients (pts) 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 loss of OZA response in pts who discontinued OZA and switched to placebo (PBO) in the TN maintenance period (MP). Methods: In TN, pts were randomized to once-daily oral OZA 0.92 mg or PBO or to open-label OZA during a 10-week induction period (IP). Pts with clinical response to OZA at Week 10 were rerandomized to OZA (OZA-OZA) or PBO (OZA-PBO) in the MP through Week 52. Disease relapse was defined as an increase in partial Mayo score (PMS) of ≥2 points vs 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 OZA-OZA and OZA-PBO pts who entered the MP after achieving clinical remission (CRM) or clinical response (CRS only, excluding pts in CRM) at Week 10. Results: In the TN MP, 230 pts continued OZA (CRM, n=82; CRS only, n=148) and 227 pts switched to PBO (CRM, n=79; CRS only, n=148). Baseline characteristics were generally similar between groups. Pts in CRS only at Week 10 had a numerically higher proportion with severe disease and prior immunosuppressive medication use vs CRM pts (Table). Differences in disease relapse between groups became apparent after MP Week 8, after which a significantly higher proportion of OZA-OZA pts were without relapse vs OZA-PBO pts (Figure). MP Week 42 Kaplan-Meier (KM) estimates of no relapse were 86.1% and 62.6% for OZA-OZA and OZA-PBO pts, respectively. Additionally, pts in CRM at Week 10 had higher rates of nonrelapse during the MP vs those in CRS only at MP entry. KM estimates of non-relapse at MP Week 42 were 67.9% and 59.7% in OZA-PBO pts with CRM and CRS, respectively, and 90.9% and 83.4% in OZA-OZA pts with CRM and CRS, respectively. Conclusion: This analysis shows that OZA is effective at preventing disease relapse over 42 weeks of maintenance treatment in pts who achieve clinical response at Week 10. These data show that OZA maintains disease control even in the event of temporary discontinuation. However, extended discontinuation should be minimized in clinical practice.Figure 1 Table 1. - Baseline characteristics in pts in CRM vs pts in CRS only at Week 10 Pts in CRM a at IP Week 10 Pts in CRS b only at IP Week 10 OZA-PBO (n=79) OZA-OZA (n=82) OZA-PBO (n=148) OZA-OZA (n=148) Age, years, mean ± SD 45.0 ± 13.5 42.7 ± 13.9 42.0 ± 13.8 42.3 ± 13.4 Males, n (%) 45 (57.0) 41 (50.0) 77 (52.0) 76 (51.4) Years since UC diagnosis, mean ± SD 7.3 ± 7.0 7.4 ± 7.2 7.2 ± 7.3 8.9 ± 7.4 Prior therapies, n (%) 5-ASA CS Immunomodulator Anti-TNF Non-anti-TNF biologic 75 (94.9)51 (64.6)24 (30.4)13 (16.5)3 (3.8) 81 (98.8)54 (65.9)26 (31.7)15 (18.3)9 (11.0) 146 (98.6)117 (79.1)61 (41.2)52 (35.1)30 (20.3) 146 (98.6)109 (73.6)63 (42.6)61 (41.2)33 (22.3) Complete Mayo score c >9, n (%) 12 (15.2) 19 (23.2) 51 (34.5) 76 (51.4) Mayo endoscopic score = 3 (severe), n (%) 22 (27.8) 25 (30.5) 94 (63.5) 107 (72.3) Fecal calprotectin, median IQR, mg/kg 1027.8 (295.0, 2689.3) 851.6 (251.4, 2694.6) 1085.2 (434.4, 2579.3) 1285.0 (486.5, 2673.4) All data are reported at IP baseline.aCRM was defined as complete Mayo score of ≤2 with no individual subscore of >1 point.bCRS was defined as decrease from baseline of ≥3 points and at least 30% in the complete Mayo score and a decrease of ≥1 in RBS or an absolute RBS of ≤1.cThe sum of the rectal bleeding subscore, stool frequency subscore, Physician’s Global Assessment subscore, and endoscopy subscore.ASA, aminosalicylic acid; CRM, clinical remission; CRS, clinical response; CS, corticosteroid; IP, induction period; SD, standard deviation; TNF, tumor necrosis factor.