Ozanimod Treatment for MS Helps Prevent Cognitive Decline Over 1 Year

Among patients with early relapsing multiple sclerosis (MS), treatment with ozanimod helps prevent cognitive decline during 1 year of use, according to study results presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2025, held in West Palm Beach, Florida from February 27 to March 1.

Patients with relapsing MS can experience impaired cognitive function early in the disease course.

Researchers conducted an interim analysis of ENLIGHTEN (ClinicalTrials.gov Identifier: NCT04140305), a 3-year prospective, multicenter, open-label study of ozanimod 0.92 mg in patients with early relapsing MS, and reported changes in cognitive function among the participants at 1 year.

Participants in ENLIGHTEN have been diagnosed with relapsing MS for less than 5 years, receive ≤1 disease-modifying therapy (DMT), have an Expanded Disability Status Scale (EDSS) score of 3.5 or greater, and have 10 or fewer gadolinium-enhancing lesions at baseline.

The researchers assessed cognitive function at baseline and annually using the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test Second Edition (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R); meaningful improvement on the SDMT was defined as an increase of 4 or more points or a 10% or greater increase from baseline. A mixed-effects model with repeated measures was employed for statistical analysis.

Overall, 177 patients completed follow-up at 1 year (mean age, 39.7 years [SD, 10.7]; women, 78.5%; White, 84.7%). Most patients (71.8%) had not received a DMT. Mean scores were as follows:

• SDMT: baseline, 53.2 (SD, 11.6); 1 year, 57.0 (SD, 12.4)
• CVLT-II: baseline, 53.6 (SD, 10.8); 1 year, 56.3 (SD, 11.9)
• BVMT-R: baseline, 24.7 (SD, 7.0); 1 year, 24.6 (SD, 7.2)

From baseline to 1 year, the mean percentage change in scores were 9.6% (SD, 32.5), 6.2% (SD, 18.1), and 3.7% (SD, 36.4) for SDMT, CVLT-II, and BVMT-R, respectively. For SDMT, clinically meaningful improvement was observed in 48.1% of participants. Least square (LS) mean change from baseline to 1 year were 3.4 (95% CI, 2.1-4.8) for SDMT, 2.7 (95% CI, 1.5-4.0) for CVLT-II, and –0.0 (95% CI, –1.0 to 0.9) for BVMT-R.

“Among patients with early [relapsing MS], of whom 71.8% were DMT-naive, ozanimod treatment prevented cognitive decline during the first year of use,” the researchers concluded.