True North: Ozanimod benefits in ulcerative colitis evident in various populations

A post hoc analysis of the phase III True North study showed that the benefits of ozanimod on clinical remission and response in patients with moderate-to-severe ulcerative colitis (UC) as seen in the global analysis were consistent in the analysis of the North American cohort.

The multicentre (285 sites in 30 countries) True North study involved 1,012 patients with moderate-to-severe UC who were randomized to receive once-daily oral doses of ozanimod (1 mg) or placebo (double-blind in cohort 1, open-label ozanimod in cohort 2) during a 10-week induction phase. At 10 weeks, patients with clinical response to ozanimod were re-randomized 1:1 to receive ozanimod (1 mg/day) or placebo double-blind until week 52 (maintenance phase; n=457).

A total of 247 patients were enrolled in North America, of whom 107 and 60 received ozanimod and placebo, respectively, in the double-blind cohort during the induction phase. Prior biologic treatment for UC was documented in 41.1 and 48.3 percent of ozanimod and placebo recipients, respectively.

At week 10, more patients in the ozanimod than placebo group achieved clinical remission (15.9 percent vs 3.3 percent). [AIBD 2021, abstract P035]

More patients on ozanimod vs placebo also achieved clinical response (46.7 percent vs 15.0 percent) and endoscopic improvement (26.2 percent vs 10.0 percent).

Among patients previously exposed to tumour necrosis factor (TNF) inhibitors, more ozanimod than placebo recipients experienced clinical response (35.7 percent vs 11.5 percent). However, ozanimod did not exert a greater effect than placebo on clinical remission or endoscopic improvement in this group. In contrast, ozanimod fared better than placebo for all three endpoints in patients without prior TNF inhibitor exposure.

A total of 105 patients in the North American study population were re-randomized in the maintenance phase, 56 and 49 to ozanimod and placebo, respectively. At week 52, more patients in the ozanimod than placebo group experienced clinical remission (39.3 percent vs 12.2 percent), clinical response (58.9 percent vs 26.5 percent), and endoscopic improvement (50.0 percent vs 16.3 percent). These benefits with ozanimod were consistent regardless of previous TNF inhibitor exposure.

Prior analysis of the global population demonstrated a benefit with ozanimod over placebo for clinical remission in the induction (18.4 percent vs 6.0 percent; p<0.001) and maintenance phases (37.0 percent vs 18.5 percent; p<0.001). Clinical response was also improved with ozanimod vs placebo in the induction (47.8 percent vs 25.9 percent; p<0.001) and maintenance phases (60.0 percent vs 41.0 percent; p<0.001). [N Engl J Med 2021;385:1280-1291]

“In this post-hoc analysis, consistent with the global population, ozanimod treatment for up to 52 weeks in North American patients with moderately-to-severely active UC showed benefits on clinical and endoscopic endpoints,” the researchers said.

The impact of prior biologic exposure

In a separate post hoc analysis of the global population, the effects of ozanimod were consistent regardless of prior treatment with biologics in the maintenance phase of the study.

Of the 992 patients included in the induction cohort analysis, 616 were biologic-naïve, while 162 and 214 had prior exposure to one and ≥2 biologics*, respectively. Patients with prior exposure to biologic treatment also had more prior corticosteroid use, longer disease duration, and more extensive disease than biologic-naïve patients.

At week 10, more ozanimod than placebo recipients achieved clinical remission, though greater impact was noted in those who were biologic-naïve (23 percent [ozanimod] vs 6.6 percent [placebo]), compared with those on one (17.2 percent vs 8.3 percent) or ≥2 prior biologics (3.7 percent vs 2.5 percent). [AIBD 2021, abstract P031]

Clinical response was noted in more ozanimod than placebo recipients (biologic-naïve: 53 percent vs 28 percent; one biologic: 50 percent vs 33 percent; ≥2 biologics: 27 percent vs 15 percent).

During the maintenance phase, clinical response, while greater with ozanimod vs placebo, was comparable in patients who were biologic-naïve and those with prior exposure to one or ≥2 biologics (61, 60, and 55 percent, respectively). Clinical remission at week 52 was similar between ozanimod recipients with exposure to one or ≥2 biologics (28 and 26 percent, respectively).

Endoscopic improvement and mucosal healing in ozanimod recipients were also similar between patients with exposure to one biologic and biologic-naïve patients.

The benefits of ozanimod vs placebo on all these endpoints during the induction and maintenance phases were evident regardless of biologic exposure in patients with insufficient response to prior anti-TNF agents, vedolizumab, or both at baseline.

“Ozanimod improved clinical, endoscopic, and histologic outcomes in both biologic-exposed and -naïve patients. Patients with prior biologic use may require additional time to respond to treatment,” the researchers noted.

*anti-TNF agent, vedolizumab, or both