RESEARCH HIGHLIGHTS Nature Reviews Neurology advance online publication 1 April 2014; doi:10.1038/nrneurol.2014.61
MULTIPLE SCLEROSIS
Could simvastatin slow down secondary progressive MS? Statins might provide a safe and inexpensive treatment option for secondary progressive multiple sclerosis (MS), which is currently intractable. According to the results from the MS-STAT phase II trial, published in The Lancet, a high dose of simvastatin—a common hypercholesterolaemia drug with a favourable safety profile—can slow down brain atrophy, which is frequently observed in late-stage MS. Many patients with relapsing–remitting MS will eventually develop a progressive form of the disease, which accounts for most of the disability burden in patients with MS. Although multiple immunomodulatory pharmacotherapies are available for relapsing–remitting MS, no drug has been previously shown to efficiently alleviate the progressive, neurodegenerative form of the disease. A team led by Jeremy Chataway from the National Hospital for Neurology and Neurosurgery (London, UK) randomly assigned 140 patients with late-stage, progressive MS to either placebo or simvastatin (80 mg per day). MRI scans were obtained at baseline, 12 months and 25 months. “Our main measure of success was to reduce the rate of brain atrophy,” explains Chataway. Brain atrophy is considered to be a biological marker for MS progression and disability. In the progressive stage of MS, the brain shrinks by about 0.6% a year. In contrast with placebo-treated patients, those who received a high dose of simvastatin showed a lower annualized atrophy rate of 0.3% a year, indicating a 43% reduction after adjustment for baseline factors such as sex and disability. Although the trial was not designed to test how simvastatin affects clinical outcomes, a small but significant effect on disability scores was observed at the 2-year follow-up: the increase in these scores was smaller in the simvastatin group than in the placebo group, suggesting that simvastatin could alleviate MS-associated disability. “The results present a very encouraging first step towards developing treatment for progressive MS,” comments Chataway. Despite the consistently slower brain atrophy rate in the simvastatin group throughout the study period, no difference was observed in immunological markers. According to Chataway, a non-immunological mechanism of action, possibly through vascular or endothelial functions, could explain the effects of simvastatin in patients with secondary progressive MS. At this stage, the results should be interpreted with caution. “The brain imaging findings might not necessarily translate into clinical benefit,” Chataway remarks. “However, our promising results warrant further investigation in larger, phase III disability-driven trials.” Hemi Malkki Original article Chataway, J. 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. Lancet doi:10.1016/S0140-6736(13)62242-4
NATURE REVIEWS | NEUROLOGY
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
MULTIPLE SCLEROSIS
Could simvastatin slow down secondary progressive MS? Statins might provide a safe and inexpensive treatment option for secondary progressive multiple sclerosis (MS), which is currently intractable. According to the results from the MS-STAT phase II trial, published in The Lancet, a high dose of simvastatin—a common hypercholesterolaemia drug with a favourable safety profile—can slow down brain atrophy, which is frequently observed in late-stage MS. Many patients with relapsing–remitting MS will eventually develop a progressive form of the disease, which accounts for most of the disability burden in patients with MS. Although multiple immunomodulatory pharmacotherapies are available for relapsing–remitting MS, no drug has been previously shown to efficiently alleviate the progressive, neurodegenerative form of the disease. A team led by Jeremy Chataway from the National Hospital for Neurology and Neurosurgery (London, UK) randomly assigned 140 patients with late-stage, progressive MS to either placebo or simvastatin (80 mg per day). MRI scans were obtained at baseline, 12 months and 25 months. “Our main measure of success was to reduce the rate of brain atrophy,” explains Chataway. Brain atrophy is considered to be a biological marker for MS progression and disability. In the progressive stage of MS, the brain shrinks by about 0.6% a year. In contrast with placebo-treated patients, those who received a high dose of simvastatin showed a lower annualized atrophy rate of 0.3% a year, indicating a 43% reduction after adjustment for baseline factors such as sex and disability. Although the trial was not designed to test how simvastatin affects clinical outcomes, a small but significant effect on disability scores was observed at the 2-year follow-up: the increase in these scores was smaller in the simvastatin group than in the placebo group, suggesting that simvastatin could alleviate MS-associated disability. “The results present a very encouraging first step towards developing treatment for progressive MS,” comments Chataway. Despite the consistently slower brain atrophy rate in the simvastatin group throughout the study period, no difference was observed in immunological markers. According to Chataway, a non-immunological mechanism of action, possibly through vascular or endothelial functions, could explain the effects of simvastatin in patients with secondary progressive MS. At this stage, the results should be interpreted with caution. “The brain imaging findings might not necessarily translate into clinical benefit,” Chataway remarks. “However, our promising results warrant further investigation in larger, phase III disability-driven trials.” Hemi Malkki Original article Chataway, J. 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. Lancet doi:10.1016/S0140-6736(13)62242-4
NATURE REVIEWS | NEUROLOGY
ADVANCE ONLINE PUBLICATION © 2014 Macmillan Publishers Limited. All rights reserved
