Eight-point Reliable Change on Symbol Digit Modalities Test with Ozanimod: Findings from the Phase 3 SUNBEAM and DAYBREAK Extension Trials
John DeLuca1, Jeffrey Cohen2, Bruce Cree3, Giancarlo Comi4, Ludwig Kappos5, Chun-Yen Cheng6, James Sheffield6, Jon Riolo6, Andrew Thorpe6, Ralph Benedict7
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, 4Vita-Salute San Raffaele University and Casa di Cura Igea, Milan, Italy, 5Research 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, 6Bristol Myers Squibb, Princeton, New Jersey, 7Jacobs MS Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York
Objective:
To evaluate long-term effects of ozanimod on cognitive processing speed (CPS) in participants with relapsing multiple sclerosis (RMS) using a Symbol Digit Modalities Test (SDMT) change of 8 points.
Background:
In the SUNBEAM trial (NCT02294058), ozanimod improved CPS versus interferon β-1a (IFN) based on ≥4-point SDMT improvement. Recently, it was suggested that an 8-point SDMT change better represents statistically reliable individual-level change.
Design/Methods:
The double-blind SUNBEAM trial randomized adults with RMS to oral ozanimod 0.92mg/d or 0.46mg/d or intramuscular IFN 30µg/wk for ≥12 months. Completers were eligible for an open-label extension (OLE) trial (DAYBREAK; NCT02576717) of ozanimod 0.92mg. We analyzed the percentage of participants with ≥8-point SDMT improvement or worsening compared with SUNBEAM baseline at SUNBEAM M12 (SUN-M12), OLE-M12, OLE-M36, and OLE-M60 in those randomized to ozanimod 0.92mg/d or IFN. P-values are nominal.
Results:
Among SUNBEAM participants (n=397, ozanimod 0.92mg; n=395, IFN) who entered the OLE, mean (SE) baseline SDMT scores were 48.0 (0.69) and 47.4 (0.68), respectively. At SUN-M12, 16.1% (64/397) and 9.1% (36/395), respectively, had ≥8-point SDMT improvement (P=0.005), and 11.6% (46/397) and 11.6% (46/395), respectively, worsened ≥8 points (P=0.970). At OLE-M12, 21.2% (84/396) of those who received continuous ozanimod improved and 17.0% (66/388) of those who started on IFN improved (P=0.219); 11.6% (46/396) and 13.1% (51/388), respectively, worsened (P=0.580). At OLE-M36, 22.5% (81/360) and 18.1% (62/342), respectively, improved (P=0.291); 13.6% (49/360) and 14.0% (48/342), respectively, worsened (P=0.674). At OLE-M60, 24.5% (79/323) and 19.7% (60/304), respectively, improved (P=0.320); 14.6% (47/323) and 15.8% (48/304), respectively, worsened (P=0.885).
Conclusions:
Compared with the IFN group, participants in the ozanimod group were significantly more likely to achieve 8-point SDMT improvement at SUN-M12. When IFN-treated participants switched to ozanimod, statistical group differences disappeared. After both SUNBEAM and the OLE (6–7 years total), the proportion of participants with 8-point improvement in the continuous-ozanimod group remained numerically higher.