Results have been published from a phase II, placebo-controlled clinical trial of high-dose oral simvastatin (Zocor, a therapy for high cholesterol) involving 140 people with secondary-progressive MS suggesting that this pill was well tolerated and able to slow the rate of brain atrophy (shrinkage) over two years. Those who took 80 mg of simvastatin, versus those who took placebo, showed 43% less brain atrophy. In their paper, the investigators, led by Dr. Jeremy Chataway (University College London), suggest that a phase III trial of simvastatin is warranted (The Lancet, early online March 19, 2014). The safety and benefit of statins in MS would need to be confirmed in phase III studies; previous results have been mixed.
Background: While there are therapies available for people with relapsing forms of MS, there are few options for people with primary-progressive MS or for those who have transitioned from relapsing MS into the secondary-progressive form of the disease.
In addition to lowering cholesterol, statins can dampen immune responses that are involved in MS, and they have shown benefits in mouse models of MS. There have been suggestions that statins have cell-protecting qualities, and so may protect against nervous system damage in MS. For these reasons, statins have previously been tried, alone or in combination with interferon beta, in relapsing MS, with mixed results. In some studies, treatment has worsened disease activity. The usual dosage to treat high cholesterol is 5 to 40 mg per day, versus the high dose of 80 mg tested in MS.
The Study: This was an investigator-initiated study at three centers in the United Kingdom which was funded through a number of government and foundation sources in the UK, and did not involve sponsorship from any pharmaceutical company. This study involved 140 people aged 18-65 years old with secondary-progressive MS. They were randomly divided into two groups, one to receive simvastatin for two years, and one to receive placebo for two years. The study was double-blinded, meaning that none of the participants, doctors, or assessors knew whether the participants were on active therapy or placebo. Participants underwent yearly MRI scanning to record whole-brain volume, as well as various tests of disability including the EDSS, a standard outcome measure of MS progression.
After two years, those on simvastatin showed less brain atrophy than those on placebo. Those on simvastatin had an average brain atrophy rate of 0.288% per year versus 0.584% in those on placebo. This represents 43% less atrophy in the simvastatin group, which was found to be statistically significant. This was the primary outcome measure of the trial. Simvastatin also had small but statistically significant impact on some measures of clinical progression. Both groups were found to have similar rates of adverse events, suggesting that simvastatin was well tolerated.
Conclusions: This phase II clinical trial found that simvastatin may hold promise for treating people with secondary-progressive MS, for whom there are few treatment options. The investigators caution that even though brain atrophy has been linked to disability in MS, the benefit against brain atrophy shown in this trial may not translate into clinical benefit. This and other potential benefits and risks could be further discovered in a phase III clinical trial of simvastatin in secondary-progressive MS, which the investigators believe is warranted. At this point there is insufficient evidence to recommend statins for the treatment of MS.