Researchers have found that administering a drug for multiple sclerosis (MS) significantly improves cognitive processing speed in patients who have secondary progressive MS compared with placebo, according to a new study.
The medication, known as siponimod, demonstrated clinical benefit over placebo, with an estimated hazard ratio of 0.79 (95% CI:0.65-0.95), or a relative risk reduction of 21%.
“While there are currently no drugs on the market in the United States 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 study author Ralph H. B. Benedict, PhD, a professor of neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York, and colleagues.
Siponimod modulates the sphingosine-1-phosphate (S1P) receptor. The drug exhibits specificity for the S1P1 and S1P5 subtype and easily crosses the blood brain barrier. Siponimod reduced confirmed disability progression in patients who have progressive MS when compared with placebo. Researchers posit that the drug may directly reduce inflammation and promote remyelination in the central nervous system.
“The overall findings from this study in a population with advanced neurological disability suggest that treatment with siponimod beneficially impacts cognitive functioning as measured by the Symbol Digit Modalities Test, a benefit likely to have a high impact on quality of life and vocational status,” the study’s authors wrote.
|The overall findings from this study in a population with advanced neurological disability suggest that treatment with siponimod beneficially impacts cognitive functioning as measured by the Symbol Digit Modalities Test.|
The study was published online December 16, 2020, in Neurology.
The neurodegenerative effects of MS compromise cognitive function, which can hinder patients’ ability to conduct activities of daily living, drive, hold gainful employment, and even shop online. Patients with progressive forms of the disease tend to experience these signs more severely.
|We are impressed to see that siponimod may improve cognitive processing speed in people with MS.|
Nearly 20% of patients in the placebo group and roughly 10% percent of patients in the siponimod group switched to open-label siponimod treatment. The placebo group had 135 patients opt to cease treatment; 57 patients in the siponimod group ended treatment.
“We are impressed to see that siponimod may improve cognitive processing speed in people with MS, however more research is needed to confirm our results,” said Dr. Benedict.
He cautioned, “Because we did not see changes on two other cognitive tests, more research should further examine how siponimod affects scores on a broader array of thinking and memory tests. This research is needed before prescribing siponimod for cognition can be considered.”
Side effects that occurred more frequently in patients taking siponimod versus placebo included high blood pressure, higher levels of liver enzymes, eye swelling, shingles, and convulsions.
One feature of the study design that distinguished it from other MS studies that evaluate neuropsychological properties is that investigators did not prescreen trial enrollees or exclude them for various conditions known to alter the cognitive development and cognitive abilities. Examples of such conditions include childhood learning disabilities as well as neurological and psychiatric disorders such as bipolar disorder and traumatic brain injury. For this reason, the study conveys the advantage of reflecting what the study’s authors refer to as “a typical secondary progressive MS population.” This distinguishing feature, however, comes with the risk of creating potential biases resulting from the inclusion of patients who exhibit these traits.
A limitation of this study is that researchers collected no demographic data such as educational background or presence of common MS symptoms such as fatigue, depression, or visual impairment as the primary outcome of the study.
The study was funded by Novartis Pharma AG, maker of siponimod. Dr. Benedict has consulting and speaking relationships with Novartis.