Effects of Ozanimod on Cognitive Processing Speed: Findings From the Phase 3 SUNBEAM and DAYBREAK Extension Trials
John DeLuca1, Jeffrey A. Cohen2, Bruce A. C. Cree3, Chun-Yen Cheng4, James K. Sheffield4, Jon V. Riolo4, Diego Silva4, Giancarlo Comi5, Ludwig Kappos6
1Kessler Foundation, West Orange, New Jersey, and Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark, New Jersey, 2Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, 3Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, 4Bristol Myers Squibb, Princeton, New Jersey, 5Vita-Salute San Raffaele University, and Casa di Cura del Policlinico, Milan, Italy, 6Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland
Objective:
To evaluate the long-term effects of ozanimod on cognitive processing speed (CPS) in relapsing multiple sclerosis (RMS) patients over 60 months (M).
Background:
In the phase 3 SUNBEAM trial (NCT02294058), ozanimod treatment improved CPS vs interferon β-1a (IFN), as measured with the Symbol Digit Modalities Test (SDMT), in participants with RMS over 12M.
Design/Methods:
In the double-blind, double-dummy, SUNBEAM trial, adults (18‒55 years) with RMS were randomized to once-daily oral ozanimod 0.92 or 0.46mg, or weekly intramuscular IFN 30µg. SUNBEAM continued until the last participant was treated for 12M; completers were eligible for an open-label extension (OLE) trial (DAYBREAK‒NCT02576717) of ozanimod 0.92mg. This exploratory analysis reports the percentage of participants with clinically meaningful (≥4 point) SDMT improvement or worsening relative to SUNBEAM baseline at 12M, and at OLE M12, M36, and M60 in those initially randomized to ozanimod 0.92mg or IFN.
Results:
SUNBEAM participants (n=397, ozanimod 0.92mg; n=395, IFN) who entered the OLE were analyzed. Mean (SE) baseline SDMT scores were 48.0 (0.69) and 47.4 (0.68), respectively. At SUNBEAM M12, 34.5% (137/397) and 27.8% (110/395) of participants randomized to ozanimod 0.92mg and IFN, respectively, had SDMT improvement, and 23.2% (92/397) and 28.1% (111/395) worsened. At OLE M12, improvement was seen in 43.2% (171/396) of those who received continuous ozanimod and 34.8% (135/388) of those originally assigned to IFN; 19.9% (79/396) and 24.7% (96/388) worsened, respectively. At OLE M36, 40.0% (144/360) and 40.1% (137/342) improved; 23.1% (83/360) and 28.1% (96/342) worsened. At OLE M60, 41.5% (134/323) and 36.8% (112/304) improved; 26.0% (84/323) and 27.3% (83/304) worsened.
Conclusions:
The percentage of participants with CPS improvement increased during the first 2‒3 years of ozanimod treatment, then maintained with continuous ozanimod treatment. The percentage of participants with CPS improvement who previously received IFN reached a similar proportion within 3 years after switching to ozanimod.