Brain atrophy and associations with long-term disability and cognitive function in participants with relapsing multiple sclerosis treated with ozanimod: Results from phase 3 and open-label extension trials.

Background: In phase 3 trials, ozanimod reduced brain atrophy and improved cognitive processing speed compared with interferon β-1a (IFN) in participants with relapsing multiple sclerosis (RMS).

Objectives: To assess long-term brain volume changes and associations with clinical/cognitive outcomes during an open-label extension ([OLE] DAYBREAK [NCT02576717]).

Methods: Completers of phase 3 "parent" trials were eligible to receive ozanimod 0.92 mg in DAYBREAK. Whole brain, thalamic, and cortical gray matter volumes (WBV, TV, and CGMV, respectively) were analyzed annually.

Results: Participants receiving continuous ozanimod had sustained, low rates of WBV loss through OLE month (M)60 (annualized least-squares mean percent change from parent baseline: RADIANCE, -0.27; SUNBEAM, -0.35). Compared with participants switched from IFN, these participants had lower reductions in WBV (parent baseline through OLE M48 [RADIANCE] and OLE M60 [SUNBEAM]). Larger baseline brain volumes were associated with numerically better Symbol Digit Modalities Test scores and lower 3-month confirmed disability progression (CDP) incidence. Annualized TV atrophy ⩽1.0% was associated with lower 3-month CDP.

Conclusion: This study confirms the sustained efficacy of ozanimod in reducing brain atrophy rates for up to 7 years. Brain volume preservation was associated with faster cognitive processing speed and slower physical disability progression.