DOP39 Endoscopic, histologic, and combined outcomes with reinitiation of ozanimod after temporary discontinuation: 2-year interim analysis of the True North open-label extension study
Vermeire, S.(1)*;Dignass, A.(2);Colombel, J.F.(3);Jain, A.(4);Canavan, J.B.(4);Wu, H.(4);Lawlor, G.(4);Osterman, M.T.(4);Rubin, D.T.(5);Regueiro, M.(6);
(1)University of Leuven, Chronic Diseases and Metabolism, Leuven, United States;(2)Agaplesion Markus Hospital- Goethe University, Medicine, Frankfurt, Germany;(3)Icahn School of Medicine of Mount Sinai, Gastroenterology, New York, United States;(4)Bristol Myers Squibb, Clinical Research, Princeton, United States;(5)University of Chicago Medicine Inflammatory Bowel Disease Center, Gastroenterology, Chicago, United States;(6)Cleveland Clinic, Digestive Disease and Surgery Institute, Cleveland, United States;
Background
Mucosal healing, evaluated by a combination of endoscopic and histologic examinations, is a desired outcome in ulcerative colitis (UC), but few long-term or open-label extension (OLE) studies of UC treatments have assessed these outcomes. In the phase 3 True North (TN) study, ozanimod 0.92 mg once daily demonstrated efficacy and safety for up to 52 weeks in patients with moderately to severely active UC. The current analysis evaluated long-term endoscopic and histologic endpoints in patients who reinitiated ozanimod after experiencing disease relapse when rerandomised to placebo during the TN maintenance period (MP).
Methods
Responders to ozanimod 10-week induction therapy were rerandomised 1:1 to ozanimod (n=230) or placebo (n=227); this OLE interim analysis (data cutoff: 10 January 2022, the point at which the OLE Week 94 disposition is available for patients) included all patients who relapsed on placebo during the MP and reinitiated ozanimod in the OLE. Endpoints included percentages of patients with endoscopic improvement (endoscopic subscore of ≤1 point), histologic remission (Geboes index score <2), and mucosal healing (endoscopy subscore of ≤1 point and Geboes index score <2) at OLE Weeks 46 and 94. Data were evaluated as observed case (OC) and nonresponder imputation (NRI) analyses.
Results
Seventy-seven (34%) patients rerandomised to placebo experienced a disease relapse in the TN MP. Median time to relapse was 12.7 weeks. At data cutoff, all 77 patients had either completed OLE Week 94 (51.9%) or discontinued treatment. At OLE Week 46, endoscopic improvement, histologic remission, and mucosal healing were achieved by 50%, 56%, and 42% of patients, respectively (OC analysis). Proportions with these endpoints further increased to 60%, 68%, and 48%, respectively, by OLE Week 94. Per NRI analysis, endoscopic improvement, histologic remission, and mucosal healing at OLE Weeks 46 and 94 were observed in 30% and 27%, 31% and 25%, and 23% and 17% of patients, respectively (Figure). Furthermore, 52% of patients with endoscopic improvement at OLE Week 46, 58% of patients with histologic remission at OLE Week 46, and 44% of patients with mucosal healing at OLE Week 46 continued to sustain the respective endpoints at OLE Week 94 with another year of ozanimod treatment.
Conclusion
In patients who experienced disease relapse after rerandomisation to placebo, reinitiation of ozanimod was associated with recapture of response and long-term endoscopic and histologic benefits, including histologic remission and mucosal healing. These data suggest that patients who experience disease relapse when ozanimod is temporarily discontinued may benefit from resumption of ozanimod treatment.