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.

Brain and Mind Centre University of Sydney Camperdown NSW Australia

Bristol Myers Squibb Princeton NJ USA

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Center for Neurology Łódź Poland

Collegium Medicum Department of Neurology University of Warmia and Mazury Olsztyn Poland

Department of Neurology and Center for Clinical Neuroscience 1st Medical Faculty and General University Hospital Charles University Prague Czech Republic

Department of Neurology and Neurological Sciences Beckman Center for Molecular Medicine Stanford University Medical Center Stanford CA USA

Department of Neurology Centre d'Esclerosi Múltiple de Catalunya Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacký University Olomouc Olomouc Czech Republic

Department of Physical Medicine and Rehabilitation and Department of Neurology and Neurosciences Rutgers New Jersey Medical School Newark NJ USA

Kessler Foundation West Orange NJ USA

Mellen Center for MS Treatment and Research Cleveland Clinic Cleveland OH USA

NeuroRx Research and Montréal Neurological Institute McGill University Montréal QC Canada

Research Center for Clinical Neuroimmunology and Neuroscience Basel Departments of Head Organs Spine and Neuromedicine Clinical Research Biomedicine and Biomedical Engineering University Hospital and University of Basel Basel Switzerland

Vita Salute San Raffaele University and Casa di Cura Igea Milan Italy

Weill Institute for Neurosciences Department of Neurology University of California San Francisco San Francisco CA USA

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ClinicalTrials.gov
NCT02576717