Background: Ozanimod reduced whole brain volume (WBV), cortical grey matter volume (CGMV), and thalamic volume (TV) loss vs interferon beta-1a (IFN) in phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) trials.
Objectives: To evaluate brain volume loss among SUNBEAM/RADIANCE participants who entered an ongoing extension trial (DAYBREAK, NCT02576717).
Methods: The 2 randomized, double-blind trials compared oral ozanimod 0.92 and 0.46 g/day with intramuscular IFN 30 µg/week in adults with relapsing MS. SUNBEAM continued until the last enrolled participant was treated for 12 months. RADIANCE was 24 months in duration. Completers were eligible to receive open-label ozanimod 0.92 mg/day in DAYBREAK. MRI was performed at months 6 (SUNBEAM), 12 (SUNBEAM/RADIANCE), and 24 (RADIANCE), then every 12 months (DAYBREAK). Baseline WBV and CGMV were measured using SienaX, and TV using ThalamicVolume software; percentage change in WBV, CGMV, and TV was quantified using Jacobian integration. Data are reported through DAYBREAK month 36.
Results: DAYBREAK includes 2257 SUNBEAM/RADIANCE participants. Loss of WBV, CGMV, and TV was less on ozanimod than IFN and remained less after switching from IFN to ozanimod, especially for WBV and TV. CGMV was lost to a much greater extent while on IFN, and recovered substantially, but not completely, upon switching to ozanimod.
Conclusions: Switching from IFN to ozanimod reduced the rate of WBV, CGMV, and TV loss. Global and regional brain volume loss after 4 to 5 years of follow-up remained higher in participants who started on IFN than in continuous ozanimod users. These results support early treatment with ozanimod.