Whole Brain, Cortical Grey Matter, and Thalamic Volume Changes During 5–7 Years of Ozanimod in Relapsing MS: Final Results from the DAYBREAK Open-label Extension Study
Jeffrey A. Cohen1, Douglas L. Arnold2, John DeLuca3, Hans-Peter Hartung4, Ludwig Kappos5, Giancarlo Comi6, Krzysztof W. Selmaj7, Lawrence Steinman8, Amit Bar-Or9, Xavier Montalban10, Eva K. Havrdová11, James K. Sheffield12, Chahin Pachai12, Chun-Yen Cheng12, Jon V. Riolo12, Bruce A. C. Cree13
1Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA, 2NeuroRx Research and Montréal Neurological Institute, McGill University, Montréal, Quebec, Canada, 3Kessler Foundation, West Orange, New Jersey, and Department of Physical Medicine & Rehabilitation and Neurology & Neurosciences, Rutgers - New Jersey Medical School, Newark, New Jersey, USA, 4Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Medical University of Vienna, Vienna, Austria; and Department of Neurology, Palacký University Olomouc, Olomouc, Czech Republic, 5Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Headorgans, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 6Vita-Salute San Raffaele University, and Casa di Cura Igea, Milan, Italy, 7Center for Neurology, Łódź, Poland and Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland, 8Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, USA, 9Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA, 10Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain, 11Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty and General University Hospital, Charles University, Prague, Czech Republic, 12Bristol Myers Squibb, Princeton, New Jersey, USA, 13Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA
Objective:
To evaluate rates of brain volume loss (BVL) among ozanimod-treated participants with relapsing multiple sclerosis (RMS).
Background:
Ozanimod significantly reduced loss of whole brain volume (WBV), cortical grey matter volume (CGMV), and thalamic volume (TV) vs interferon beta-1a (IFN) in participants with RMS from the phase 3 SUNBEAM (NCT02294058) and RADIANCE (NCT02047734) studies.
Design/Methods:
Patients who completed SUNBEAM/RADIANCE (“parent” studies) were eligible for ozanimod 0.92 mg/d in the DAYBREAK open-label extension (OLE) (NCT02576717). WBV and CGMV (SienaX) and TV (ThalamicVolume) were measured annually through M60 (SUNBEAM database lock: 4/7/2023; RADIANCE ad hoc brain volume data transfer: 2/22/2024. Least squares mean (LSM) % and annualized LSM% change from parent baseline (P-BL) or OLE-BL in volumes were quantified using Jacobian Integration and adjusted mixed-model analyses.
Results:
DAYBREAK included 2257 participants. Continuous ozanimod led to stable and low rates of WBV loss through OLE M60 (annualized LSM% change from P-BL: RADIANCE, −0.27; SUNBEAM, −0.35). Compared with participants who switched from IFN, continuous ozanimod led to significantly (nominal P<0.05) lower LSM% reductions in WBV from P-BL through OLE M48 (RADIANCE) and OLE M60 (SUNBEAM). In RADIANCE participants, switching from IFN to ozanimod reduced rates of WBV loss (annualized LSM% change from P-BL to RADIANCE M24 and OLE-BL to OLE M24: −0.48 and −0.19, respectively); a similar pattern was observed in SUNBEAM participants and for annualized LSM% change in TV. While high annualized LSM% reductions in CGMV were observed with IFN (SUNBEAM P-BL to M12: −1.02; RADIANCE P-BL to M24: −0.59), lower annualized LSM% CGMV loss was observed after 12 months of ozanimod in the OLE.
Conclusions:
Ozanimod treatment led to decreased BVL during SUNBEAM/RADIANCE, which was sustained with continuous treatment up to 5 years in the OLE. Switching from IFN to ozanimod consistently reduced rates of BVL; participants continuously treated with ozanimod had lower WBV loss.
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