SPMS Drug Linked to Improved Cognition Processing Speed, Study Says

As a neurodegenerative disease, secondary progressive multiple sclerosis (SPMS) may lead to a degradation of cognition skills as the disease progresses.

Patients with secondary progressive multiple sclerosis (SPMS) taking siponimod for 1 to 2 years had improved cognitive processing speed compared with those who did not, according to a recent study.

The study, a post-hoc analysis of the EXPAND phase 3 randomized controlled trial (RCT) comparing siponimod and placebo, was published in Neurology.

The trial involved 1651 patients with SPMS randomized (2:1) to either siponimod 2 mg/day or placebo. The patients, with an average age of 48, were followed for up to 2 years.

Cognitive function was assessed using the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT) and Brief Visuospatial Memory Test-Revised (BVMT-R), administered at baseline, 6-month intervals, and end of treatment.

The SDMT measures cognitive processing speed; the test-taker is given a key of symbols matched to numbers. They are then shown a series of symbols and must say the corresponding number for each symbol as quickly as possible. The test result is the number of items correctly answered in 90 seconds.

Researchers found that on average the group of people taking siponimod improved their scores on this test after 1 year, 18 months, and again at 2 years.

In patients given a placebo, the scores stayed the same.

No drug is approved for improving the cognition of patients with MS, but given that the brain degenerative disease does affect thinking skills, it is an area of concern and research. Another drug for SPMS, ozanimod, has also been shown to improve cognition.

In this study, patients taking siponimod had a 28% higher chance of having a sustained improvement of 4 or more points compared with placebo.

An increase or decrease of 4 or more points is considered clinically meaningful and is linked with quality of life outcomes and disability progression.

Those in the siponimod group also had a 21% lower chance of having a 4-point or lower decrease in score.

Among all participants:

  • 35% of those taking siponimod improved their scores by 4 or more points, compared with 27% of people taking a placebo
  • 41% taking siponimod had no change compared with 42% taking a placebo
  • 25% taking siponimod had lower scores by 4 or more points compared with 32% of people taking a placebo

However, the scores on the 2 other thinking and memory tests, the PASAT and BVMT-R, did not differ between the 2 groups (all P >.28).

Side effects that occurred more frequently in siponimod versus placebo included high blood pressure, higher levels of liver enzymes, eye swelling, shingles, and convulsions.


Benedict RHB, Tomic D, Cree BA, et al. Siponimod and cognition in secondary progressive multiple sclerosis: EXPAND secondary analyses. Neurology. Published online December 16, 2020. doi: 10.1212/WNL.0000000000011275