Slowing the Progression of Multiple Sclerosis With Statins

Researchers in the United Kingdom have shown a reduction in the rate of brain atrophy progression with use of 80-mg simvastatin daily in patients with secondary-progressive multiple sclerosis over a 2-year period.

Results of the phase-2 MS-STAT trial indicate that the cholesterol-lowering drug simvastatin may reduce the progression of brain atrophy in patients with secondary-progressive multiple sclerosis (SPMS).^1,2

SPMS is a subtype of multiple sclerosis that occurs after the initial phase of MS, relapsing-remitting multiple sclerosis (RRMS). RRMS includes relapsing episodes punctuated by gradual worsening in the baseline symptoms of the disease.³

Over approximately 25 years, RRMS progresses to SPMS in approximately 90% of patients. In patients with SPMS, relapses are superimposed over progressively worsening baseline symptoms between each relapse.³

Until now, no treatment has shown a definitive effect on slowing the course of disease progression in patients with SPMS. The phase-2 MS-STAT trial included 140 patients with SPMS between the ages of 18 and 65. Patients received 80 mg of simvastatin daily (n = 70) or placebo (n = 70). Over the trial course, assessments of efficacy occurred at months 1, 6, 12, and 24.¹

In a press release, lead author Dr Jeremy Chataway noted the primary endpoint, stating, "Our main measure of success was to reduce the rate of brain atrophy."

MRI scan results indicate a reduction in the rate of atrophy with simvastatin treatment versus placebo of 0.254 percentage points—0.288% (standard deviation [SD] 0.521) in the treatment group vs 0.584% per year (SD 0.498) in the placebo group. Stated another way, that result corresponds with a 43% relative risk reduction in atrophy progression when adjusting for demographic differences between the placebo and treatment groups.^1,2

It is important to note that the MS-STAT study results diverge from the earlier findings of a larger study that investigated the effect of simvastatin in patients with RRMS. In this large study, known as SITCOMBIN, of 307 patients with RRMS, 151 received interferon beta plus simvastatin and the remaining 156 patients received interferon beta with placebo. Results of the analysis showed no significant benefit with simvastatin on MRI measures, disability measures, or time between relapses over a treatment period up to 3 years in length.⁴

Although trials have shown divergent results in different populations of patients with MS to date, patients with SPMS may benefit from simvastatin treatment, whereas add-on simvastatin treatment may not benefit patients with RRMS.^1,4

The results of this phase-2 trial are promising, although as noted by Professor and Dean Alan Thompson, “a phase-3 trial will be essential to confirm the results.”

Ultimately, results of further investigation will be necessary to inform clinicians and regulatory agencies on whether or not simvastatin is a safe and effective treatment for SPMS.

References:

• Chataway J, Schuerer N, Alsanousi A, et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014.
• University College of London Hospitals. Statins could hold key in battle against multiple sclerosis. www.uclh.nhs.uk/News/Pages/Statinscouldholdkeyinbattleagainstmultiplesclerosis.aspx. Accessed March 2014.
• Hurwitz BJ. The diagnosis of multiple sclerosis and the clinical subtypes. Ann Indian Acad Neurol. 209;12(4):226-230.
• Sorensen PS, Lycke J, Erälinna JP, et al; for SIMCOMBIN study investigators. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011;10(8):691-701.