Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS

Mult Scler Relat Disord. 2021 Feb;48:102673. doi: 10.1016/j.msard.2020.102673. Epub 2020 Dec 10.


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; Cognition; Multiple sclerosis; Neuropsychological tests; Ozanimod.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Humans
  • Indans
  • Interferon beta-1a / therapeutic use
  • Middle Aged
  • Multiple Sclerosis*
  • Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Neuropsychological Tests
  • Oxadiazoles
  • Young Adult


  • Indans
  • Oxadiazoles
  • Interferon beta-1a
  • ozanimod

Associated data

  • ClinicalTrials.gov/NCT02294058