Multiple Sclerosis Relapse Activity After Ozanimod Discontinuation in DAYBREAK Trial Participants.
Gold R, Selmaj KW, Berkovich R, Cohen JA, Comi G, Havrdová EK, Sheffield JK, Desai H, Cheng CY, Riolo JV, Thorpe A, DeBoer E, Cree BAC.Ann Clin Transl Neurol. 2026 Mar 27. doi: 10.1002/acn3.70366. Online ahead of print
Objective: Return of disease activity is expected when patients discontinue disease-modifying therapy (DMT) for multiple sclerosis (MS). Some MS DMTs are associated with higher-than-expected disease activity (rebound) after discontinuation. This exploratory analysis assessed disease activity and risk of rebound after ozanimod discontinuation.
Methods: DAYBREAK (NCT02576717; October 2015-April 2023) was a single-arm, open-label extension trial of ozanimod 0.92 mg/d in participants with relapsing MS who completed phase 1-3 ozanimod trials. Two protocol amendments increased the required safety follow-up from an initial 28 days to 75 and then 90 days. Confirmed post-treatment relapses were characterized.
Results: Of 2494 participants, 1679 participants had ≥ 1 day of follow-up and did not initiate commercial ozanimod in ≤ 14 days of exiting the trial; 30.6% had ≤ 60 days of post-treatment follow-up. Fifty-five participants (3.3%) had known post-treatment relapse. Fifty-four were not taking an MS DMT when they relapsed; one relapsed soon after starting fingolimod. Relapses were associated with Expanded Disability Status Scale (EDSS) score increases of 0-3 points (median 1 point); the participant with the 3-point increase had a moderate relapse and complete recovery in 23 days. Forty-two participants (76.4%) fully recovered, 11 (20.0%) partially recovered, and 2 (3.6%) did not recover. Only one (1.8%) relapse was considered severe by the investigator: EDSS increased from 7.5 to 8.0, and the participant partially recovered within 36 days.
Interpretation: Most participants did not relapse within 90 days following ozanimod discontinuation. Post-treatment relapse cases suggestive of a rebound effect were not observed.
Source: multiple-sclerosis-research.org