There are more than 20 disease-modifying therapies( DMTs) for treating relapsing forms of multiple sclerosis( MS), including active secondary-progressive MS( SPMS). However, only one therapy is approved for primary-progressive MS( PPMS). And to date, none have been shown to be effective in managing non-relapsing SPMS.
Because each type of MS behaves differently, studying DMTs for MS is challenging, much more so for progressive MS than relapsing MS. One reason for the disparity is that relapsing MS involves a major inflammatory response, one you can see on an MRI scan, says Professor Jeremy Chataway, MA, PhD, FRCP.“ But progressive neurodegeneration has multiple mechanisms and is incompletely understood,” he told NARCOMS Now.
Professor Chataway is a Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square( part of University College London Hospitals NHS Foundation Trust), and Professor of Neurology at University College London.
“ We’ re going through the mist in some ways, trialing out medications and trying to get a combination of treatments. It’ s hard. Obviously, you can’ t do biopsies as you can in organ systems, but advanced imaging is coming along,” explains Professor Chataway.“ There are a number of reasons, and it’ s really hard to work out the biology in vivo. Animal models are good, but not perfect, so we have incomplete information. We need to get where we are with relapsing-remitting MS( RRMS), but we’ re not there at all with progressive MS.”
RECENT CLINICAL TRIAL RESULTS
Clinical trials are essential in assessing the safety and efficacy of experimental therapies.
Even when outcomes are unexpected or disappointing, they contribute to our understanding of MS and help guide future directions in research, as demonstrated by some of the most recent trials in progressive MS.
PHASE 3 MS-STAT2 TRIAL ON SIMVASTATIN
In the previous Phase 2 trial 1, 140 participants with SPMS received either 80 mg / day of simvastatin or placebo. The double-blind controlled trial demonstrated a significant reduction in whole brain atrophy( loss of brain tissue) over two years compared to placebo. Simvastatin, a prescription drug used to decrease low-density lipoprotein( LDL) cholesterol in the blood, was also well tolerated.
These promising results led to the Phase 3 MS-STAT2 2 trial involving almost 1,000 participants. Researchers set out to determine if simvastatin could slow disability progression in people with SPMS. The primary outcome was to evaluate if 80 mg / day of simvastatin versus placebo would affect disability progression at six months based on an Expanded Disability Status Scale( EDSS) score compared with a baseline score.
At the six-month mark, the research team found that simvastatin did not slow disability progression in people with SPMS.“ Certainly, in my mind, this says that simvastatin does not have a role in ameliorating progressive MS. I think that may be true of all statins, but that’ s a personal view,” says Professor Chataway, the chief investigator of the MS-STAT2 trials.
“ We were trying to see, in the context of this trial, if we could reduce progression, and we did not. That’ s not to say that cholesterol management is not important in progressive MS, just that statins don’ t look to be the right approach to have an effect on MS in general. There have also been a number of trials in RRMS, and statins did not reduce the relapse rate. No matter which way you cut it, I don’ t think statins have a role in MS per se.”
These trial results suggest that researchers can put statins aside and investigate other promising options. However, Professor Chataway stresses the importance of statins for many people to treat vascular comorbidities in MS. Research shows that vascular comorbidity is associated with greater risk of disability progression in people with MS. 3
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