Efficacy of ozanimod by patient response trajectory subgroups identified using group-based trajectory modelling: a post hoc analysis of the phase 3 True North study

Background : Ozanimod (OZA) is approved for the treatment of moderately to severely active ulcerative colitis in adults. A previous post hoc analysis of the phase 3 True North (TN) trial identified 5 discrete groups of patient (pt)-response trajectories to OZA using group-based trajectory modelling (GBTM). Objectives: This analysis further evaluated symptomatic, clinical, and mucosal outcomes in these groups. Methods : Five trajectory groups were identified by GBTM using change from baseline (BL) in partial Mayo score in pts on continuous OZA until W52 (OZA/OZA; N=229): super-response (Group 1; n=38), sustained improvement (Group 2; n=85), partial improvement (Group 3; n=60), fast rebound (Group 4; n=25), and slow rebound (Group 5; n=21) (Schreiber et al. Am J Gastroenterol. 2023;118:S671–2). Symptomatic remission and response were evaluated in each group through W52, and results were compared vs placebo (PBO). Clinical and mucosal endpoints (EPs) were evaluated at W10 and/or W52 using nonresponder imputation analysis. Results : Significantly more pts in Group 1 vs PBO achieved early symptomatic response on Day (D) 5 (34.2% vs 11.1%; P=0.0002) and remission on D6 (10.5% vs 2.8%; P=0.0264). Symptomatic EPs were sustained for 52 wk in Groups 1–3. Groups 4 and 5 started losing symptomatic efficacy by W18 ([ Fig. 1 ]). The highest proportions of symptomatic remission at W10 were achieved in Groups 1 and 2 (97.4% and 75.3%) and were sustained until W52 (73.7% and 64.7%) (Fig. 1a); similarly, ~100% of pts in Groups 1 and 2 achieved symptomatic response by W10 and it was sustained in >80% of pts until W52 (Fig. 1b). Generally, Groups 1>2>3 had sustained or increased rates of clinical and mucosal EPs from W10 to W52. Groups 4 and 5 had decreased rates of clinical and mucosal EPs at W52 (Table). Corticosteroid (CS)-free remission at W52 was greatest in Groups 1>2>3. Analysis of BL parameters showed that Group 1 had the least prior CS (60.5%), immunomodulator (26.3%), and anti–tumor necrosis factor use (23.7%). Fig. 1 (A) Symptomatic remissiona and (B) symptomatic response until TN W52 by GBTM-identified pt-response patterns Fig. 2 Conclusion : This analysis shows 3 distinctly different OZA populations within the responders, with Group 1 achieving symptomatic response as early as D5. Early response was related to long-term benefits, with Group 1 (and to a lesser extent with Groups 2 and 3) being more likely to achieve disease control at W52 with OZA. These findings show the utility of personalized medicine to direct therapeutic choice but need confirmation in future prospective cohorts. Publication History Article published online: 26 September 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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