P316 Ozanimod is an efficacious oral therapy after 5-ASA failure in immunomodulator- and biologic-naive patients with ulcerative colitis: post hoc analysis from True North
Sands, B.E.(1);Dignass, A.(2);Irving, P.(3);Chiorean, M.(4);Long, M.(5);Eren, D.(6);Ahmad, H.A.(6);Osterman, M.T.(6);Petersen, A.(6);Elegbe, A.(6);Ritter, T.(7);Danese, S.(8);
(1)Icahn School of Medicine at Mount Sinai, Gastroenterology, New York, United States;(2)Goethe University, Gastroenterology, Frankfurt, Germany;(3)Guy’s and St Thomas’ NHS Foundation Trust, Gastroenterology, London, United Kingdom;(4)Swedish Medical Center, Gastroenterology, Seattle, United States;(5)UNC Chapel Hill, Gastroenterology, Chapel Hill, United States;(6)Bristol Myers Squibb, Department of Immunology and Fibrosis Development, Princeton, United States;(7)GI Alliance, Gastroenterology, Southlake, United States;(8)IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Tbc, Milan, Italy;
Background
Oral 5-aminosalicylates (5-ASA) and corticosteroids (CS) are often the first-line treatment for ulcerative colitis (UC), and patients (pts) who fail these agents typically advance to chronic immunosuppressives. Ozanimod, an oral sphingosine 1-phosphate receptor modulator, is approved for treating adults with moderately to severely active UC in the US. This post-hoc analysis from the pivotal phase 3 True North randomised controlled trial evaluated the efficacy of ozanimod at week (wk) 10 (end of induction) in immunomodulator- and biologic-naive pts with moderate to severe UC who failed 5-ASA with or without concomitant CS.
Methods
True North consisted of a 10-wk induction period. Pts in Cohort 1, stratified by CS use at screening, were randomised to either ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg; n=429) or placebo (n=216) once daily in a double-blind manner; pts in Cohort 2 (n=367) received open-label daily ozanimod 0.92 mg. At enrollment, pts were required to be on stable doses of oral 5-ASA and/or CS for >2 wk and continued on the same dose throughout induction. Pts who received tofacitinib within 2 wk of screening were excluded. This analysis focused on clinical remission, clinical response, endoscopic improvement, and mucosal healing efficacy outcomes in immunomodulator- and biologic-naive, 5-ASA exposed pts.
Results
Of 464 pts treated with 5-ASA and were immunomodulator- and biologic-naive, with or without CS, 205 were on ozanimod and 105 were on placebo in Cohort 1; 158 received open-label ozanimod in Cohort 2. Baseline characteristics were similar between groups in Cohort 1. Compared with placebo at wk 10, a higher proportion of ozanimod-treated patients achieved clinical remission (23.4% vs 8.9%), clinical response (53.7% vs 30.7%), endoscopic improvement (35.6% vs 14.9%), and mucosal healing (18.0% vs 5.0%; Figure 1) in this subgroup. These results are consistent with previously published results of the overall study population,1 which demonstrated significantly greater proportions of patients receiving ozanimod vs placebo achieving clinical remission (18.4% vs 6.0%), clinical response (47.8% vs 25.9%), endoscopic improvement (27.3% vs 11.6%), and mucosal healing (12.6% vs 3.7%). Additionally, all efficacy endpoints were achieved by a greater proportion of patients on ozanimod vs placebo regardless of CS use at baseline (Figure 2). Results were similar for open-label ozanimod-treated patients in Cohort 2.
Conclusion
Ozanimod demonstrated efficacy at wk 10 in immunomodulator- and biologic-naive patients with UC who had failed 5-ASA, regardless of CS use at baseline.
1N Engl J Med 2021;385:1280.
