P773 Extended induction in the True North open-label extension study: clinical outcomes of ~2 years of ozanimod treatment
Vermeire, S.(1)*;Colombel, J.F.(2);Chiorean, M.V.(3);Ghosh, S.(4);Jain, A.(5);Lawlor, G.(5);Osterman, M.T.(5);Wu, H.(5);Canavan, J.B.(5);Rubin, D.T.(6);
(1)University of Leuven, Chronic Diseases and Metabolism, Leuven, Belgium;(2)Icahn School of Medicine of Mount Sinai, Gastroenterology, New York, United States;(3)Swedish Gastroenterology, Gastroenterology, Issaquah, United States;(4)University of Birmingham, Immunology and Immunotherapy, Birmingham, United Kingdom;(5)Bristol Myers Squibb, Clinical Research, Princeton, United States;(6)University of Chicago Medicine Inflammatory Bowel Disease Center, Gastroenterology, Chicago, United States;
Ozanimod is approved in the EU, US, and other countries for the treatment of moderately to severely active ulcerative colitis in adults. In the phase 3, 52-week, double-blind True North (TN) study, Week 10 clinical nonresponders to ozanimod could enter the open-label extension (OLE) to continue treatment. Previous analysis showed that approximately 50% of Week 10 nonresponders achieved symptomatic clinical response with extended induction during the OLE in as early as 5 weeks. The current analysis evaluated long-term clinical and symptomatic endpoints up to 2 years in this delayed responder subgroup.
Efficacy data were analysed for TN Week 10 ozanimod nonresponders who subsequently received open-label ozanimod in the OLE, both by whole subgroup and original study arms (double-blind [Cohort 1] and open-label ozanimod [Cohort 2]) (data cutoff: January 10, 2022). Endpoints included symptomatic clinical response, symptomatic clinical remission, total Mayo score, clinical response, clinical remission, and corticosteroid (CS)-free remission up to OLE Week 94 (104 weeks of continuous ozanimod treatment). Data were evaluated using observed case (OC) and nonresponder imputation (NRI) analyses.
A total of 226 nonresponders at TN Week 10 entered the OLE (Cohort 1, n=150; Cohort 2, n=76). Males comprised 67% of this subgroup, and mean (SD) age was 39.6 (13.6) years. Symptomatic clinical response (Figure 1), symptomatic clinical remission, and reduction in partial Mayo scores were observed as early as OLE Week 5 and were maintained through OLE Week 94. Minimal change in total Mayo score was observed from TN Week 0 (baseline) to TN Week 10 (OLE Week 0), but significant reductions from baseline occurred by OLE Week 46 (–4.2 [2.7]) and OLE Week 94 (–5.3 [2.6]). Overall, 62% of patients achieved clinical response, 26% achieved clinical remission, and 24% achieved CS-free remission at OLE Week 46; these increased to 74%, 35%, and 33%, respectively, by OLE Week 94 in the OC analysis (Figure 2). Data were similar between Cohorts 1 and 2.
Symptomatic response in ozanimod nonresponders was observed as early as 5 weeks after extended induction with ozanimod. Delayed response to ozanimod was maintained for up to 2 years as demonstrated by both symptomatic and objective endpoints. Even in those with delayed initial response, efficacy of ozanimod was durable.