Abstract
Background
Cognitive dysfunction, including slowed cognitive processing speed (CPS), is one of the most disabling symptoms of multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT) is a preferred measure of CPS for MS trials and routine screening. Based on encouraging SDMT results in the phase 3 SUNBEAM trial, these post hoc, exploratory analyses were conducted to further compare effects of the sphingosine 1-phosphate receptor modulator ozanimod versus intramuscular interferon β-1a on CPS in participants with relapsing multiple sclerosis (RMS).
Methods
In the phase 3, double-blind, double-dummy, SUNBEAM study, adults (aged 18‒55 years) with RMS (N=1,346) were randomized to once-daily oral ozanimod 0.92 or 0.46 mg, or weekly intramuscular interferon β-1a 30 µg. The study continued until the last participant was treated for 12 months. CPS was measured as part of a secondary endpoint using the SDMT. Exploratory, post hoc analyses evaluated SDMT change and percentages of participants with clinically meaningful (≥4-point) SDMT improvement or worsening at months 6 and 12, and relationship between SDMT and brain volume on magnetic resonance imaging.
Results
Ozanimod improved SDMT scores compared with interferon β-1a at months 6 and 12. At month 12, least squares mean difference in SDMT z-scores for ozanimod 0.92 mg versus interferon β-1a was 0.102 (95% CI, 0.031‒0.174, nominal p = 0.0051; standardized mean difference = 0.1376). A greater percentage of ozanimod 0.92 mg‒treated participants had clinically meaningful improvements in SDMT scores versus interferon β-1a at month 6 (30.0% versus 22.2%) and month 12 (35.6% versus 27.9%). Of those with SDMT improvement at month 6, 66.4% of those treated with ozanimod 0.92 mg and 55.9% of those treated with interferon β-1a had sustained improvement at month 12. Brain volume loss was similar for those with SDMT improvement versus worsening at month 12.
Conclusions
In these exploratory analyses, ozanimod had modestly beneficial effects on CPS in RMS participants. The effects of ozanimod on SDMT are being further evaluated in an ongoing 3-year clinical trial. SUNBEAM is registered on clinicaltrials.gov (NCT02294058) and the European Clinical Trials Database (EudraCT 2014‐002320‐27).
Keywords
Brain volume; Multiple sclerosis; Ozanimod
Bibliographic citation
DeLuca J, Schippling S, Montalban X, Kappos L, Cree BAC, Comi G, et al. Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS. Mult Scler Relat Disord. 2021 Feb;48:102673.
Audience
Professionals
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https://hdl.handle.net/11351/7759This item appears in following collections
- CEMCAT - Articles científics [106]
- HVH - Articles científics [2972]
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