Real-world data reflect promising efficacy, safety of ozanimod for UC

The first-in-class sphingosine-1-phosphate receptor modulator ozanimod showed promising efficacy and safety in a relatively treatment-refractory cohort of patients with ulcerative colitis (UC), according to the initial results of a prospective, observational cohort study presented at the Crohn’s and Colitis Congress 2022.

“At present, there is no real-world data showing the effectiveness in UC. This is the first report,” said Dr Nathaniel Cohen from the University of Chicago Medical Center Digestive Diseases Research Core Center, Chicago, Illinois, US, during his presentation.

The study comprised 29 consecutive patients (median age 41 years, 56 percent male, median disease duration 5 years) who have initiated ozanimod therapy at the research team’s tertiary centre. Of these, 26 patients had UC, one had indeterminate colitis, one had Crohn’s colitis, and one had lymphocytic colitis. Nearly half (48 percent) of participants had left-sided colitis, 44 percent had extensive colitis, while 67 percent had previous biologic exposure. Only UC patients were included in the efficacy analysis.

At week 2, half of the participants demonstrated clinical response, a third were in remission, while a quarter achieved corticosteroid(CS)-free remission. Week 4 saw a similar trend, with 50 percent having a clinical response, 23 percent achieving remission, and 18 percent achieving CS-free remission. By week 10, the corresponding rates were 53, 29, and 24 percent, respectively.

“Of note, there was a mean percentage reduction in absolute lymphocyte count of around 72 percent, and all patients who had data at weeks 0 and 4 had >60-percent reduction in lymphocyte count,” said Cohen. “This is expected, considering the mechanism of action of this particular therapy,” he added.

Of the seven patients who reported adverse events, five (ie, acute gastroenteritis, fatigue, nausea, mild liver derangement, chest pain) resolved or remained mild, and did not require discontinuation of ozanimod. One patient who developed hypertensive urgency required ozanimod cessation. One patient who reported fatigue and headache had improved symptoms upon stopping ozanimod treatment.

“In conclusion, we present the first real-world data of ozanimod in treatment-refractory UC patients and described good effectiveness in a large cohort of well-treated patients, and a safety profile that is not different from that described in the clinical trials,” concluded Cohen. “Longer follow-up in larger patient cohorts is required to assess ozanimod’s role in clinical practice.”

These findings support the results of the pivotal phase III True North trials, which have comprehensively evaluated ozanimod. The results of these trials consequently led to the FDA approval of ozanimod for moderate-to-severe active UC. [N Engl J Med 2021;385:1280-1291; Am J Gastroenterol 2020;115:S3,S6-S8; Am J Gastroenterol 2021;116:S8-S9]