In this study, high-dose simvastatin reduced the annualized rate of whole-brain atrophy in secondary progressive MS.
Secondary progressive multiple sclerosis, for which no satisfactory treatment presently exists, accounts for most of the disability in patients with MS. Simvastatin-which is widely used for treatment of vascular disease-has both immunomodulatory and neuroprotective properties that make it a potential candidate drug for patients with secondary progressive MS.
In a phase 2 study, a double-blind, placebo-controlled trial undertaken at 3 centers in the UK, patients aged 18 to 65 years with secondary progressive MS were randomly assigned to receive either 80 mg of simvastatin or placebo.1 MS patients, treating physicians, and outcome assessors were masked to treatment allocation. The primary outcome was the annualized rate of whole-brain atrophy measured from serial volumetric MRI.
One hundred forty participants were randomly assigned to receive either simvastatin (n=70) or placebo (n=70). The mean annualized atrophy rate was significantly lower in MS patients in the simvastatin group (0•29% per year) than in those in the placebo group (0•58% per year). Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events.
In conclusion, the trial showed that high-dose simvastatin reduced the annualized rate of whole-brain atrophy compared with placebo, and was well tolerated and safe in patients with secondary progressive MS.
Key Points About Statins and MS
• Brain atrophy is a biomarker that captures loss of neurons and axons, but it is unclear to what extent reducing brain atrophy will result in delaying disease progression in terms of clinical disability.• There have been other trials of statins in MS that have
shown a protective effect. We need to understand the mechanism of action of simvastatin and whether it is working via MS-specific mechanisms, or whether it is targeting vascular comorbidities that are associated with MS disease progression. It is important to identify the mechanisms before this treatment strategy is taken forward to phase 3 clinical trials.
1. 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. The Lancet. 19 March 2014.