Simvastatin for secondary progressive MS Phase III
Simvastatin is being tested as a treatment for secondary progressive multiple sclerosis (SPMS). It is taken as a tablet once daily.
- Simvastatin reduces inflammation and may have neuroprotective effects
- In a phase II study in SPMS, simvastatin reduced the rate of brain tissue loss by 43% compared to placebo
- No significant side effects have been reported from MS studies.
How does simvastatin work?
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 is not known how simvastatin might be reducing the loss of brain tissue and slowing down progression in SPMS, but there is evidence that statins reduce inflammation and have neuroprotective effects. It is also recognised that cardiovascular problems are linked to greater disability in MS, so the benefits of simvastatin seen in SPMS could be a direct result of lower cholesterol and improvement in cardiovascular health.
How is simvastatin taken?
Simvastatin is taken as a tablet, once daily. The dose of simvastatin used in MS studies is at the top end of the dose range normally recommended for lowering blood levels of cholesterol.
What are the results so far?
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. They suggest that there might be a lag in the effect of statins. The results suggest that statins might slow down progression in MS. 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. Further studies - such as MS-STAT2 - will be needed to confirm these results.
- MS-STAT1 – simvastatin compared to placebo in secondary progressive MS
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 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.
What further research is planned?
- MS-STAT2 – simvastatin compared to placebo in secondary progressive MS
This phase III study is investigating the potential benefits of simvastatin further. The researchers aim to recruit 1180 participants with SPMS at study centres in the UK who will take 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 will be an increase in EDSS which lasts for 6 months or more. Participants will also be monitored for other measures of MS progression and will be asked to complete questionnaires to measure the impact of MS on their day-to-day living.
The study is still recruiting participants. You can find out more about the study on the University College London website.
Register your interest in taking part by completing a short questionnaire.
Estimated completion date August 2023.
Further details of this study.
No significant side effects of simvastatin were reported in the MS-STAT1 study.
Common side effects of statins can include nosebleeds or a runny or blocked nose, sore throat, headache, nausea or digestive problems and muscle and joint pain.
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.
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.
- American Journal of Health System Pharmacy 2012;69(17):1494-1499. Summary Efficacy of statins in combination with interferon therapy in multiple sclerosis: a meta-analysis.
- The Lancet 2014;383(9936):2213–2221. Full article Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.
- Cochrane Database of Systematic Reviews 2011;(12):CD008386. Full article Statins for multiple sclerosis.
- CNS Drugs. 2015 Apr;29(4):277-91. Summary Statin treatment in multiple sclerosis: a systematic review and meta-analysis.
- Mult Scler Relat Disord. 2019 Feb;28:193-196. Summary Therapeutic lag in reducing disability progression in relapsing-remitting multiple sclerosis: 8-year follow-up of two randomized add-on trials with atorvastatin.