Treatment with oral ozanimod (Zeposia) reduced markers of intestinal inflammation among patients with moderately to severely active ulcerative colitis, confirming previously demonstrated clinical benefits.
Levels of fecal calprotectin declined by 68.7% at week 8 among patients receiving ozanimod, 0.5 mg per day, and by 70% for those receiving 1 mg per day, compared with 53.4% among those given placebo, according to William J. Sandborn, MD, of the University of California San Diego in La Jolla.
And at week 32, the corresponding decreases were 72.6% and 80.6%, compared with 42.3%, he reported during a poster session at the virtual Crohn’s and Colitis Congress.
Ozanimod is an oral sphingosine-1-phosphate (SIP) receptor modulator that selectively targets SIP1 and SIP5 and induces peripheral lymphocyte sequestration, which blocks the migration of proinflammatory lymphocytes from the lymph nodes to inflamed areas of the intestine. The drug was shown to be effective for active ulcerative colitis in randomized phase II and III trials. In one of those studies, clinical remission at week 10 was achieved by 18.4% of patients receiving ozanimod compared with 6% of those given placebo.
The drug was FDA approved for the treatment of multiple sclerosis in 2020.
The markers fecal calprotectin and fecal lactoferrin increase as a result of the neutrophils present in inflamed gut tissue, and correlate with gastrointestinal inflammation. To explore the effects of ozanimod on these markers, Sandborn and colleagues conducted a post-hoc analysis of data from the phase II TOUCHSTONE study, which included 197 adults whose total Mayo scores ranged from 6 to 12, and who were currently being treated with oral aminosalicylates and/or corticosteroids.
Mean age was approximately 40, mean disease duration was 6 years, and more than half were men. Mean Mayo score at baseline was 8.5.
Median fecal calprotectin levels ranged from 1,238 to 1,477 µg/g, and median fecal lactoferrin levels were 29 to 30.6 µg/g.
At week 8, patients receiving the 1-mg dose who achieved clinical remission had significantly lower levels of fecal calprotectin than nonresponders (0.029 vs 0.568, P=0.0001), as did those given the 0.5-mg dose (0.103 vs 0.381, P=0.0084). Clinical remission was defined as a total Mayo score of 2 or lower and no subscore higher than 1.
For fecal lactoferrin, decreases from baseline at week 8 were 61% in the 0.50-mg group, 84.7% in the 1-mg group, and 35.7% in the placebo group (P=0.0012 for the 1-mg dose). At week 32, the corresponding reductions were 62.5%, 85.3%, and 60.2%.
And as with fecal calprotectin, patients achieving clinical remission had significantly greater reductions in fecal lactoferrin at week 8 compared with nonresponders.
For both markers, decreases were greater for patients in the 1-mg group compared with the 0.5-mg group.
These data support the findings of the phase III True North study, in which fecal calprotectin was significantly lower in patients treated with 1 mg per day compared with placebo at weeks 10 and 52.
“The results of the current analysis demonstrate that in patients with moderately to severely active ulcerative colitis, responders and remitters to treatment with ozanimod 1 mg per day have both clinical and biomarker evidence of reduce inflammation,” Sandborn concluded.
The TOUCHSTONE study was funded by Bristol Myers Squibb (BMS).
The authors disclosed multiple relevant relationships with industry including BMS.