May 13, 2004
Laurie Barclay, MD
Simvastatin at a dose of 80 mg is associated with reduced number and volume of multiple sclerosis (MS) lesions on magnetic resonance imaging (MRI) at six months, according to the results of a preliminary open-label study published in the May 15 issue of The Lancet. Given the natural history of MS, the editorialist is cautious, pointing out the study limitations and recommending randomized trials.
"These findings suggest that an 80-mg daily dose of oral simvastatin over a six-month period could inhibit the inflammatory components of MS that lead to neurological disability," senior author Inderjit Singh, from the Medical University of South Carolina in Charleston, says in a news release. "Our results, combined with the published work on the immunological effects of statins, lend support to the case for randomized controlled clinical trials to establish the safety and efficacy of statins in the treatment of relapsing-remitting MS."
Part of the rationale for statin therapy was that many drugs have been approved for relapsing forms of MS, but they are only partly effective, need to be injected, and are expensive.
In this study, 30 patients with relapsing-remitting MS received oral simvastatin, 80 mg daily, and tolerated treatment well. Compared with the mean number of gadolinium-enhancing lesions noted on pretreatment brain MRI scans, the mean number of lesions after six months of treatment decreased by 44% (P < .0001), and total lesion volume decreased by 41% (P = .0018).
The Medical University of South Carolina and Dr. Singh have applied for licensure of a patent about use of statins for treatment of neurodegenerative and inflammatory diseases. If the patent is licensed, monies will be distributed according to the Medical University of South Carolina's intellectual property policy guidelines, with Dr. Singh entitled to 25% of the income from this patent. Merck supported this study and gave honoraria for speaking to Dr. Singh and two other authors.
In an accompanying commentary, Chris H. Polman and Joep Killestein, from the VU Medical Centre in Amsterdam, the Netherlands, call this study "a big step forward," but only an initial step in determining the potential role of statins in MS. They recommend additional trials investigating the clinical effects of statins, the optimum dose, the therapeutic window, the differential potency, and the role of combination therapy.
"Physicians, scientists, drug companies, and regulatory agencies should now work together to design and do randomised studies that have adequate power to address these and other important issues," Drs. Polman and Killestein write. "It is the joint responsibility of all involved to ensure that some of the potential charms of statins (low-hurdle access, convenience, low cost) do not develop into a dangerous boomerang, in case proper studies become jeopardised by widespread off-label use."
A review in the June issue of The Lancet Neurology also discusses the potential for statins as treatment for MS, either as monotherapy or as an add-on to established disease-modifying drugs.
"The obvious advantage of statins over existing MS therapies is their oral route of dosing," writes lead author Hans-Peter Hartung, from Heinrich Heine University in Düsseldorf, Germany. "As the evidence of the benefit of statins in MS is currently insufficient, large controlled clinical trials are needed. The first of these trials is about to start."
Lancet. 2004;363:1570, 1607-1608
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