Progressive MS Clinical Trial of Rituximab Stopped After Drug Fails to Show Effectiveness

Researchers at the National Institutes of Health (NIH) announced that a small clinical trial of a progressive multiple sclerosis (MS) treatment was stopped early due to poor results. The trial was evaluating the drug rituximab for its efficacy in depleting harmful immune cells and decreasing nerve damage in these MS patients. The results were published in an article, titled “Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis,” in the journal The Annals of Clinical and Translational Neurology.

According to the International Progressive MS Alliance (PMSA), as many as 80 percent of people with MS may develop a type of progressive form of the disease. Unlike relapsing-remitting MS (RRMS), the most common type of the disease, there are no effective therapies for progressive MS. The lack of efficacy of RRMS-targeted drugs in progressive MS patients is attributed to the fact that inflammation in progressive MS occurs in compartments of the brain and spinal cord that these drugs cannot access due to the selectivity of the blood-brain barrier.

Researchers launched a small study investigating the potential of rituximab to treat progressive MS. Rituximab, which is used to treat rheumatoid arthritis and certain cancers, depletes B cells, immune cells that are thought to play a role in the exacerbated inflammation damage observed in MS.

The clinical trial, “Double Blind Combination Rituximab by IntraVenous andIntraThecAl injection versus placebo in patients with Low-Inflammatory SEcondary progressive MS” (RIVITaLISe; NCT01212094), aimed to answer two questions: Can rituximab efficiently deplete central nervous system (CNS) B cells? and, if so, Does this lead to inhibition of CNS inflammation and slowing of CNS tissue destruction?

The study enrolled 27 people with secondary-progressive MS, who were either assigned to the rituximab group or the placebo group. Interim analyses of ongoing results, however, showed that B cells in the spinal fluid were not being depleted at a significant rate by the drug, which was interpreted as rituximab’s lack of efficacy at entering the CNS. Moreover, researchers found that the levels of axonal damage marker, neurofilament light chain, did not change in response to treatment.

In light of such results, the clinical trial was terminated. Future plans include the ongoing studies of other treatments for progressive MS. On a positive note, the drug ocrelizumab was found to achieve positive results in primary-progressive MS and relapsing MS in 2015.