Siponimod Treatment May Benefit Cognition in Advanced Multiple Sclerosis

Secondary analysis of data from the EXPAND trial (NCT01665144) of siponimod (Mayzent; Novartis, East Hanover, NJ) for treatment of secondary progressive multiple sclerosis (SPMS) showed significant benefit of siponimod on cognition. These results were published in Neurology. Siponimod treatment reduced the risk of a 4-point sustained decrease in symbol digit modalities test (SDMT) score, considered to be clinically meaningful, by 21% (95% CI, 0.65-0.96; P=.0157) and increased the chances of having a 4-point sustained increase in SDMT by 28% (95% CI 1.05, 1.55]; P=.0131).

The 1,651 individuals enrolled in the trial, mean age 48,  were randomly assigned 2 to 1 to receive siponimod 2 mg/day or placebo. Cognition was measured with the SDMT, Paced Auditory Serial Addition Test (PASAT), and Brief Visuospatial Memory Test-Revised (BVMT-R). 

After 12, 18, and 24 months of treatment, individuals treated with siponimod had mean change from baseline on the SDMT that was significantly better compared with those treated with placebo. The difference between those treated with siponimod vs placebo increased over the course of the 24-month trial. At 12 months, the difference was 1.08 points (95% CI 0.23, 1.94; P=.0132), and at months 18 and 24 respectively, the differences were 1.23 (95% CI 0.25, 2.21; P=.0135) and 2.30 points (95% CI 1.11, 3.50; P=.0002). The PASAT and BVMT-R scores did not differ significantly between those treated with siponimod vs placebo (P>0.28 for all comparisons).

“While there are currently no drugs on the market in the US approved for the treatment of cognitive impairment in MS, our study found that siponimod, which is prescribed to slow the progression of physical disability in MS, may also help improve cognitive processing speed in people with advanced MS,” said Ralph H.B. Benedict, PhD, University of Buffalo. “However, more research is needed to confirm our results.”