Of patients who failed to achieve a response at week 10 of induction in the True North trial, 50% achieved symptomatic clinical response with further ozanimod therapy in the OLE study.1,2 A related analysis evaluated outcomes at approximately 2 years in 226 patients from cohorts 1 and 2 who did not exhibit a response after 10 weeks of ozanimod induction therapy and then entered the OLE study.3 Patients had a mean age of 39.6 ± 13.6 years, and 67.3% were male. The mean age at diagnosis was 33.2 ± 13.2 years, and the mean time since UC diagnosis was 6.6 ± 6.3 years. At OLE weeks 46 and 94, ozanimod therapy was associated with clinical response rates of 62.4% and 73.8%, clinical remission rates of 26.0% and 35.3%, and rates of corticosteroid-free remission of 23.6% and 32.9%, respectively. At week 5 of the OLE study, on the basis of observed case analysis, 53.6% of patients had achieved a symptomatic clinical response, and this percentage rose to 86.3% at OLE week 94 (Figure 2). Symptomatic clinical remission was noted in 17.1% of patients at OLE week 5, and the percentage rose to 57.9% at OLE week 94. Mean total Mayo scores decreased from 9.2 at baseline to 3.8 at OLE week 94, and continuous reductions in mean partial Mayo scores were observed from baseline through OLE week 94.
Figure 2.
Symptomatic clinical response in nonresponders who entered the OLE after 10 weeks in TN: OC and NRI analyses. NRI, nonresponder imputation; OC, observed case; OLE, open-label extension; TN, True North. Adapted from Rubin et al. Abstract Tu1736. Presented at: DDW 2023; May 6-9, 2023; Chicago, Illinois.3
Data from the same True North population of 226 patients with UC were evaluated to determine endoscopic and histologic endpoints.4 The analysis included 150 patients in cohort 1 and 76 patients in cohort 2. At weeks 46 and 94, on the basis of observed case analysis, ozanimod therapy was associated with endoscopic improvement in 29.9% vs 47.7%, histologic remission in 42.0% vs 48.4%, and mucosal healing in 24.4% vs 39.1% of the 226 patients, respectively. Outcomes were generally similar in patients from cohort 1 and cohort 2.
A third study evaluated outcomes in 77 True North patients who responded to ozanimod therapy during the induction phase, were randomized to placebo for the maintenance phase, experienced relapse, and were started again on ozanimod therapy during the OLE study.5 By the time of data cutoff, 49 patients (31.2%) had withdrawn from OLE treatment, mostly because of lack of efficacy. On the basis of observed case analysis, at OLE weeks 46 and 94, rates of endoscopic improvement were 50.0% and 60.0%, rates of histologic remission were 55.8% and 67.9%, and rates of mucosal healing were 41.9% and 48.1%, respectively.
References
- Sandborn WJ, Feagan BG, D’Haens G et al. True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280–1291. doi: 10.1056/NEJMoa2033617. [DOI] [PubMed] [Google Scholar]
- Panaccione R, Afzali A, Hudesman D Extended therapy with ozanimod for delayed responders to ozanimod in moderately to severely active ulcerative colitis: data from the True North open-label extension study. Abstract OP196. 2022. Presented at: 30th United European Gastroenterology Week; October 8-11. Vienna, Austria.
- Rubin DT, Colombel JF, Chiorean MV Extended induction in the True North open-label extension study: clinical outcomes of ~2 years of ozanimod treatment. Abstract Tu1736. 2023. Presented at: DDW 2023; May 6-9. Chicago, Illinois.
- Chiorean MV, Colombel JF, Rubin DT Achievement and maintenance of endoscopic, histologic, and combined outcomes after extended induction in week 10 nonresponders of ozanimod: 2-year interim analysis of the True North open-label extension study. Abstract Tu1745. 2023. Presented at: DDW 2023; May 6-9. Chicago, Illinois.
- Regueiro MD, Dignass A, Colombel JF Endoscopic, histologic, and combined outcomes with reinitiation of ozanimod after temporary discontinuation: 2-year interim analysis of the True North open-label extension study. Abstract Tu1742. 2023. Presented at: DDW 2023; May 6-9. Chicago, Illinois.