Simvastatin was tested as a treatment to reduce progression in secondary progressive MS (SPMS). It's currently used to lower the level of cholesterol in the blood.
Unfortunately, a phase III trial (MS-STAT2) found that simvastatin had no effect on slowing disability progression in SPMS.
Simvastatin belongs to a group of drugs called statins. Statins are widely prescribed to lower the level of “bad” cholesterol in the blood and reduce the risk of diseases affecting the heart and circulation.
It was thought simvastatin might be able to reduce brain tissue loss, slow down disability progression, reduce inflammation and have neuroprotective effects. However, this was not supported in initial results from a phase III clinical trial (MS-STAT2).
Simvastatin is taken as a tablet, once daily. The dose of simvastatin used in MS studies was at the top end of the dose range normally recommended for lowering blood levels of cholesterol.
There's been an interest in the potential of statins in multiple sclerosis for some time. Four studies evaluated taking either simvastatin or atorvastatin in combination with one of the disease modifying drugs (a self-injected beta interferon); over the two years of the studies there was no difference in relapse rates or measures of disability compared to taking beta interferon alone.
However, more recently, an Italian research team went back to reassess disability levels in 69 participants 8 years later. They found that taking atorvastatin (20 or 40 mg/day) in combination with beta interferon for 2 years in the original study was linked to milder disease progression 8 years later. The researchers suggest that statins may slow down progression in MS, but there may be a lag in the effect. However, this was just a small group from the original study; of the 69 reassessed, 42 had taken beta interferon plus placebo and just 27 had taken beta interferon plus atorvastatin.
140 people with SPMS took either a high dose of simvastatin (80mg a day) or a placebo for two years. Participants were aged 18-65 and had Expanded Disability Status Scale (EDSS) scores of between 4 and 6.5.
Throughout the trial brain volume was assessed using MRI brain scans, levels of disability were assessed using the EDSS and participants completed several questionnaires that examined the impact of MS on their daily lives.
In the group taking simvastatin, brain volume loss was 43% less compared to those taking placebo. Smaller but still significant effects on two of the disability measures were also found, there was a slower change in EDSS and improved scores in the MSIS-29 questionnaire, which measures the impact of MS on daily life. However no change was found in the frequency of relapses or the scores on the MS Functional Composite Scale (MSFC), which is a measure of mobility, dexterity and cognition.
This phase III study investigated the potential benefits of simvastatin on disability progression further. The researchers recruited 964 people with SPMS at study centres in the UK. They took either simvastatin (80mg/day) or placebo for 3 years. This dose of simvastatin is at the top end of the dose range normally recommended for lowering blood levels of cholesterol.
The main measure of progression was an increase in EDSS which lasted for 6 months or more. Participants were also monitored for other measures of MS progression and were asked to complete questionnaires to measure the impact of MS on their day-to-day living.
Disappointingly, initial results, presented at ECTRIMS 2024, showed that simvastatin had no effect on reducing progression rate when compared to placebo. Simvastatin was found to be safe and well tolerated throughout the trial.
One person on the trial was admitted to hospital with serious muscle damage (rhabdomyolysis), but this resolved quickly.
You can find out more about the study on the University College London website.
No significant side effects of simvastatin were reported in the MS-STAT1 study.
Common side effects of statins can include:
Statins can occasionally cause muscle inflammation (swelling) and damage. In 2011, the US Food and Drug Administration (FDA) warned that muscle damage was more likely with the higher 80mg dose used in MS studies. There was one case of this in the MS-STAT2 trial.
People with liver problems should not take statins, nor should pregnant or breastfeeding women. Statins can interact with a number of other medications potentially increasing the risk of serious side effects such as muscle damage. Grapefruit juice can also increase the risk of experiencing side effects.
