Ozanimod Efficacious in Patients With Ulcerative Colitis Exposed to Vedolizumab

Ozanimod is efficacious in patients with moderate to severe UC who previously received treatment with vedolizumab.

Ozanimod is efficacious for treating moderate to severe ulcerative colitis (UC) in patients who have previously been exposed to vedolizumab therapy, according to study results presented at the Advances in Inflammatory Bowel Diseases (AIBD) 2022 conference, held from December 5 to 7, 2022, in Orlando, Florida.

The oral sphingosine-1-phosphate (S1P) receptor modulator, ozanimod, prevents the migration of lymphocytes to inflamed tissues and is approved for use in the setting of moderate to severe UC in the United States and the European Union. It was unclear, however, whether ozanimod would be efficacious among patients who have been exposed to vedolizumab treatment, which is an integrin receptor antagonist that interferes with lymphocyte trafficking.

In the True North study, which was a phase 3 trial, patients with UC were randomly assigned to receive 0.92 mg ozanimod or placebo (cohort 1) or open-label ozanimod (cohort 2) during the induction period. During the maintenance phase, patients who had a clinical response at week 10 were rerandomly assigned to receive ozanimod or placebo. In this posthoc analysis, the efficacy of ozanimod was evaluated among the subset of patients who were vedolizumab-experienced (N=185) using the Cochran-Mantel-Haenszel (CMH) test.

Among the subset of patients who were vedolizumab-experienced, 35 received placebo in cohort 1, 63 received ozanimod in cohort 1, and 87 received open-label ozanimod in cohort 2.

At baseline, 52% of patients had extensive disease, 78% had a Mayo score of 3, 85% were exposed to anti-tumor necrosis factor therapies, and 61% were receiving corticosteroids.

Among cohort 1, ozanimod was more effective than placebo at week 10, in which 15.9% and 8.6% had symptomatic remission, 4.8% and 2.9% had clinical remission, 28.6% and 20.0% had clinical response, 12.7% and 5.7% had endoscopic improvement, and 6.3% and 0% had mucosal healing among the ozanimod and placebo cohorts, respectively.

In the pooled analysis of ozanimod recipients in both cohorts, the clinical response rate was higher for the subset of patients who received vedolizumab as a first-line therapy (50%) compared with those who received vedolizumab as a later-line treatment (32.0%).

At week 52, patients who received ozanimod continuously vs patients who received both placebo and ozanimod had higher rates of remission (39.4% vs 4.5%; P =.005), corticoid-free remission (27.3% vs 4.5%; P =.044), clinical response (57.6% vs 22.7% P =.014), endoscopic improvement (39.4% vs 9.1%; P =.017), and mucosal healing (21.2% vs 0%), respectively.

“Ozanimod was effective in UC patients who were previously [vedolizumab-exposed], including those who failed [vedolizumab] alone or following other advanced therapies,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Sands B, Jain A, Ahmad H, et al. Efficacy of ozanimod in patients with ulcerative colitis who were previously exposed to vedolizumab: True North post-hoc analysis. Abstract presented at: AIBD 2022; December 5-7, 2022; Orlando, FL. Abstract 15.