Ozanimod, effective induction and maintenance therapy for ulcerative colitis: NEJM
USA: A recent study in the New England Journal of Medicine reported ozanimod to be more effective than placebo for the treatment of patients with moderately to severely active ulcerative colitis.
Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Ozanimod, a selective sphingosine-1- phosphate receptor modulator is under investigation for the treatment of inflammatory bowel disease.
William J. Sandborn and colleagues aimed to evaluate the efficacy and safety of ozanimod in treating inflammatory bowel disease. They conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.
In the 10-week induction period, patients in cohort 1 received oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner. Patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52).
The primary endpoint for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Key secondary clinical, endoscopic, and histologic endpoints were evaluated with the use of ranked, hierarchical testing. Safety was also assessed.
•A total of645 patients were included in cohort one study and 367 in cohort 2; a total of 457 patients were included in the maintenance period.
The results of the study were found to be:
• The incidence of clinical remission was found to be significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%,) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10]).
• The incidence of clinical response was found to be significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%) and maintenance (60.0% vs. 41.0%). All other key secondary endpoints were significantly improved with ozanimod as compared with placebo in both periods.
• The incidence of infection (of any severity) with ozanimod was observed to be similar to that with placebo during induction and higher than that with placebo during maintenance.
• Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Elevated liver aminotransferase levels were more common with ozanimod.
Dr Sandborn and the team concluded that "Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis."
The study titled, "Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis," is published in the New England Journal of Medicine.