Several post hoc analyses of the True North study, which demonstrated ozanimod efficacy and safety in patients with moderately to severely active UC, were presented.1
Two analyses focused on the impact of endoscopic disease on ozanimod effectiveness. The first assessed the impact of baseline endoscopic disease activity on clinical outcomes with ozanimod treatment in patients.2 Among the 1012 patients in the True North study, a higher proportion of patients had severe disease (60.2%) than moderate disease (39.8%) at baseline. Compared with placebo, ozanimod demonstrated significantly superior efficacy in most clinical outcomes in patients with moderate and severe endoscopic disease, regardless of disease activity at baseline. The treatment effects of ozanimod were similar for all evaluated efficacy endpoints at week 10 in patients with moderate and severe US, regardless of baseline endoscopic disease activity. At week 52, ozanimod efficacy was similar for most evaluated endpoints regardless of baseline endoscopic disease activity.
The second post hoc analysis focused on endoscopic disease and evaluated the association of baseline endoscopic disease distribution (leftsided colitis vs extensive colitis) on clinical outcomes with ozanimod.3 This analysis found that ozanimod was more effective than placebo in patients with left-sided and extensive colitis at weeks 10 and 52 for all evaluated endpoints, and this efficacy was similarly effective regardless of disease distribution. Some data suggested that patients with extensive disease at baseline may require a longer treatment time to robustly achieve more stringent histologic endpoints, but these endpoints were achieved by week 52.
A third post hoc analysis examined the safety and efficacy of ozanimod in patients according to their age group (<60 years or ≥60 years).4 Ozanimod efficacy was similar between these 2 age groups and superior to placebo regardless of age group across several efficacy endpoints, including clinical remission, clinical response, endoscopic improvement, and mucosal healing, both at week 10 and week 52. Placebo response rates were higher in older than in younger patients across all efficacy endpoints at both timepoints. As a result, the adjusted treatment differences for ozanimod vs placebo for most endpoints were lower for the older age group and none achieved statistical significance. Among older patients, ozanimod treatment was not associated with any new safety signals, and there was no evidence of higher rates of serious adverse events. The authors noted that the study had relatively few participants aged 60 years or older, so larger real-world studies may be useful.
Two post hoc analyses examined the efficacy of ozanimod according to prior treatment history. One examined ozanimod efficacy in patients who were previously exposed to vedolizumab.5 This analysis demonstrated that ozanimod was effective in patients with prior vedolizumab exposure, including those who failed vedolizumab alone, or following other advanced therapies. After 52 weeks, a significantly higher proportion of vedolizumab-exposed patients who were rerandomized to ozanimod achieved symptomatic remission, clinical response, clinical remission, corticosteroid-free remission, and endoscopic improvement compared with vedolizumab-exposed patients rerandomized to placebo.
The second post hoc analysis that focused on prior treatment history examined the efficacy of ozanimod at week 10 with or without concomitant corticosteroids among immunomodulatorand biologic-naive patients as well as patients with prior 5-aminosalicylic acid (5-ASA) exposure.6 Ozanimod was efficacious as an induction therapy in immunomodulatorand biologic-naive patients regardless of corticosteroid use at baseline. Further, ozanimod was also shown to have efficacy as induction therapy in patients with 5-ASA exposure at baseline. The incidence of adverse events was similar between placebo and ozanimod cohorts, regardless of prior corticosteroid exposure.
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]
- Wolf DC, Panaccione R, Blumenstein I et al. Ozanimod is an effective oral treatment for patients with ulcerative colitis regardless of moderate or severe endoscopic disease activity at baseline: a post hoc analysis of the phase 3 True North study [ACG abstract C0387]. Am J Gastroenterology. 2022;117(suppl 105) [Google Scholar]
- Afzali A, Dignass A, Fischer M et al. Ozanimod is an effective oral treatment for patients with ulcerative colitis regardless of baseline endoscopic disease distribution: a post hoc analysis of the phase 3 True North study [ACG abstract E0343]. Am J Gastroenterology. 2022;117(suppl 105) [Google Scholar]
- Khan N, Irving P, Blumenstein I et al. Evaluation of ozanimod efficacy and safety in older patients with ulcerative colitis: post hoc analysis from the phase 3 True North study [ACG abstract A0391]. Am J Gastroenterology. 2022;117(suppl 105) [Google Scholar]
- Sands BE, Jain A, Ahmad HA et al. Efficacy of ozanimod in vedolizumab-exposed patients with ulcerative colitis: a phase 3 True North post hoc analysis [ACG abstract B0352]. Am J Gastroenterology. 2022;117(suppl 105) [Google Scholar]
- Sands BE, Dignass A, Irving P et al. 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 [ACG abstract A0392]. Am J Gastroenterology. 2022;117(suppl 105) [PMC free article] [PubMed] [Google Scholar]