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.