One of our Sermo physician experts, Andrew Wilner, M.D., a neurohospitalist, is a regular contributor to our Multiple Sclerosis HUB. He discusses the latest treatment using statins for multiple sclerosis patients. This discussion was originally published on our Multiple Sclerosis Hub, Hubs are gathering places inside Sermo for M.D.s and D.O.s to discuss disease states.
Introduction
Multiple medications for the treatment of relapsing remitting multiple sclerosis (RRMS) have received Food and Drug Administration (FDA) approval based primarily on their ability to decrease the annual relapse rate (ARR). Numerous drugs are available for RRMS, including interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaseron), glatiramer acetate (Copaxone), the three orals; dimethyl fumarate (Tecfidera), fingolimod (Gilenya), and teriflunomide (Aubagio), and infusion therapies; natalizumab (Tysabri) and mitoxantrone (Novantrone).
However, despite conventional treatment, more than half of RRMS patients progress to a “secondary progressive” phase of the disease, where disability accumulates. Only mitoxantrone is FDA approved for secondary progressive multiple sclerosis. An improved, less toxic treatment could be considered the “holy grail” of multiple sclerosis clinical research.
A Therapeutic Breakthrough?
Jeremy Chataway, PhD, Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, University College London Hospital NHS Foundation Trust, London, UK, may have found it.
In a remarkable paper published in The Lancet, Dr. Chataway and colleagues demonstrated that simvastatin, a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, decreased the annualized rate of atrophy by 43% in 70 treated patients compared to 70 placebo controls in a two year, double blind, controlled trial (Chataway et al. 2014). At 24 months, there were also statistically significant benefits to simvastatin with respect to EDSS (Expanded Disability Status Scale) and MSIS-29 (Multiple Sclerosis Impact Scale). There was no significant difference between simvastatin and placebo in the MSFC (Multiple Sclerosis Functional Composite). The drug was well tolerated, with a similar proportion of serious adverse events in the simvastatin group (20%) vs. the placebo group (13%).
What is Simvastatin?
Simvastatin, as its name implies, is a statin, a drug class normally used for the treatment of hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, and for secondary prevention of myocardial infarction and stroke. Simvastatin received FDA approval in 1991 and is marketed as Zocor. Generic preparations are now available, costing as little as pennies a day.
Plausible Rationale
Why should statins help in multiple sclerosis? In addition to their cholesterol lowering effects, statins affect the immune system. They inhibit MHC class II-restricted antigen presentation, downregulate T-cell activation and proliferation, and shift T-helper lymphocytes from a Th1 to a Th2 phenotype, reducing inflammation. Statins also decrease leukocyte migration through the blood brain barrier. Statins have been tested as adjunctive therapy in RRMS, but failed to demonstrate convincing efficacy (Bhardwaj et al. 2012). Consequently, it is all the more surprising that simvastatin was effective in secondary progressive multiple sclerosis.
Conclusions
If simvastatin really does prevent accumulation of disability in patients with secondary progressive multiple sclerosis, it represents a dramatic therapeutic breakthrough. Such a finding would propel research efforts to learn more about the pathophysiology of multiple sclerosis as it relates to the mechanism of action of statins and perhaps result in the development of novel therapies. Because statins are widely available and inexpensive, clinicians may be inclined to prescribe them off-label to patients with secondary progressive multiple sclerosis. Although not without adverse effects, their side effect profile is well known.
The Chataway study had a limited number of patients, and these encouraging results need to be replicated in a larger trial. It may be difficult to find a sponsor, however, as the generic status of simvastatin stands to significantly limit potential profits. Indeed, this small study was sponsored by the Imperial College without direct support from the pharmaceutical industry. Hopefully, a proper Phase III clinical trial will be done in the near future to confirm or refute these exciting results.
Bio
Andrew Wilner, M.D., a neurohospitalist, is a regular contributor to our Multiple Sclerosis HUB. He also volunteers as the medical director of Lingkod Timog, a nonprofit medical mission organization that delivers health care to rural areas of the Philippines. For more information, see www.drwilner.org.
Dr. Wilner’s latest book is titled Bullets and Brains, a collection of essays on neurology and society, published in 2013. Available in paperback and Kindle e-book on Amazon.com.
References
Bhardwaj S, Coleman CI, Sobieraj DM. Efficacy of statins in combination with interferon therapy in multiple sclerosis: A meta-analysis. Am J Health Syst Pharm 2012;69:1494-1499.
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 randomized, placebo-controlled, phase 2 trial. Lancet, March 19, 2014; http://dx.doi.org/10.1016/S0140-6736(13)62242-4.
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