Statins May Be Effective for Secondary Progressive Multiple Sclerosis

S. Andrew Josephson


AccessMedicine from McGraw-Hill 

Patients with multiple sclerosis (MS) most commonly have a relapsing-remitting course followed eventually by a secondary progressive phase. During this latter period, disability relentlessly accumulates without discrete episodes of clinical or radiographic worsening. Commonly, progressive atrophy is the main feature of secondary progressive MS on brain MRI. While there are now many effective immunomodulatory therapies for relapsing-remitting MS, effective and well-tolerated treatments for the secondary progressive stage are sorely lacking. Chataway and colleagues (2014) aimed to examine whether high-dose simvastatin would be effective in secondary progressive MS.

The authors enrolled patients in a double blind, placebo-controlled, randomized trial at three centers in England. Patients age 18–65 years were enrolled if they had an Expanded Disability Severity Scale (EDSS) score between 4.0 and 6.5 and met criteria for the secondary progressive stage of the illness. Patients were excluded if they had been treated with glucocorticoids within 3 months or had received any immunosuppressive or immunomodulatory drug within 6 months of study entry. The primary outcome examined was the annualized rate of whole brain atrophy over a 2-year period as measured by serial brain MRI.

A total of 140 patients were randomized to either 80 mg of simvastatin daily or placebo. A total of 9 patients (6 in the placebo group and 3 assigned to simvastatin) were lost to follow-up. Medication compliance >90% occurred in around 77% of each treatment group. In the primary intention-to-treat analysis, there was significantly less atrophy seen in the simvastatin group than in those assigned to placebo (adjusted difference, –0.254% per year; 95% confidence interval, –0.422 to –0.087; p = .03); this value corresponds to a 43% reduction in the annualized rate of atrophy. The observed rate of atrophy in the placebo group was similar to that found in previous studies of secondary progressive MS. There was a similar reduction in atrophy favoring simvastatin found in a per-protocol analysis. An additional analysis of just the first-year MRI data also showed similar results with greater variability as expected.

Secondary analyses included a statistically significant difference in EDSS scores favoring the simvastatin group but no significant differences seen in the MS functional composite scale or in the rate of new and enlarging lesions (the latter suggesting the patients in the study indeed were in the secondary progressive stage of their illness). Adverse events were similar in the two groups, and there were no safety differences observed between the two treatments.

This intriguing study may give some hope to patients with secondary progressive MS, a phase of the illness without effective therapies. Limitations include that the study focused its primary outcome on MRI atrophy rates, rather than a clinically meaningful measure; in some other studies, however, atrophy has correlated well with clinical outcomes. In addition, patients were all taken off their immunomodulatory drugs well before the trial started, making the trial “cleaner” but at the same time prohibiting comparisons with previously available treatments. While high-dose simvastatin was well tolerated in this study, other larger trials of this dose in different settings have shown difficulties with muscle and liver complications, an important observation that will need to be explored in future MS studies. Taken as a whole, these results support a larger trial of high-dose simvastatin for secondary progressive MS but are likely not definitive enough to recommend statin treatment for these patients today.