Treatment with ozanimod (oza) attains high efficacy rates in real-world clinical practice at week 12 for advanced therapy (AT)-naive patients with moderate-to-severe ulcerative colitis (UC) and at week 26 for those with AT exposure, as shown by initial results from POLARIS, an ongoing phase IV open-label study. 

Thisfinding suggests the benefits of using oza following conventional therapies or after failing one biologic mechanism of action (MOA), according to lead study author Dr Bincy Abraham from Houston Methodist?Weill Cornell in Houston, Texas, US. 

Abraham and her team enrolled 65 patients (mean age 43.2 years, mean body mass index 27.7 kg/m2, 78.5 percent White, 15.4 percent Hispanic or Latino) in two cohorts: AT-native (ie, naive to thiopurines and any biologics; cohort 1) or AT-exposed (ie, failed one prior MOA of biologics; cohort 2). 

Clinical response at week 12 for cohort 1 and week 26 for cohort 2 was the primary endpoint. The assessment at week 26 was decided based on the historically delayed response to next-line therapies in biologic-exposed patients. 

For the secondary outcomes, Abraham and colleagues assessed clinical remission, endoscopic response, endoscopic improvement, histological improvement, and Inflammatory Bowel Disease Questionnaire (IBDQ) response and remission at weeks 12 and 26. They also examined endoscopic and histologic remission at week 26, as well as treatment-emergent adverse events (TEAEs) for safety. 

Real-world efficacy 

Baseline demographics and disease characteristics did not significantly differ between the two cohorts, but patients in cohort 2 were more likely to be male, had longer disease duration, and had a higher proportion of severe UC. [AIBD 2024, abstract S19] 

The use of corticosteroid at screening was reported in 15 patients (29.4 percent) in cohort 1 and four (28.6 percent) in cohort 2. Among AT-exposed participants, 50 percent had prior treatment with an antitumour necrosis factor while 14.3 percent had previously received vedolizumab. 

Of the patients with UC, 70.6 percent achieved the primary endpoint at week 12 in cohort 1 and 51.7 percent did so at week 26 in cohort 2. Clinical remission was reached by 31.4 percent at week 12 and by 42.9 percent at week 26. A large proportion of these patients also achieved other secondary endpoints. 

In terms of safety, nearly half of the participants (46.2 percent) reported experiencing TEAEs, with few serious ones (3.1 percent), but no drug-related TEAEs led to the discontinuation of ozatreatment. There were also no new signals seen with regard to adverse events of special interest, such as opportunistic infections, cardiovascular events, hepatic events, macular oedema, and malignancies. 

“Similar trends were observed with IBDQ endpoints, thus demonstrating early composite evidence of oza impact on quality of life,” Abraham said. “No new safety signals were identified.” 

Oza is an oral, selective sphingosine 1-phosphate receptor 1 and 5 modulator approved for the treatment of moderate-to-severe UC in adults.