“Multiple sclerosis patients may benefit from statins,” The Guardian reports.
MS is a progressive condition affecting nerves in the brain and spinal cord, causing problems with balance, vision and muscle movement.
The study looked at whether simvastatin – a type of statin – could decrease shrinking of the brain, which occurs in the later stages of MS (although not all patients will reach this stage).
Using brain scans, researchers found that people with MS who took the drug had 43% less brain shrinkage a year than those who were given a dummy treatment (placebo).
A small but statistically significant improvement in one disability scale and one symptom scale was also found. However, it is unclear if these improvements would translate into a meaningful improvement in a patient’s quality of life.
The results of this small, early stage trial are promising and warrant further research, not least because simvastatin is a lot cheaper than most current MS medication.
A larger trial (known as a phase III trial) is now needed to find out if these results would translate into any benefits for a larger number of patients.
Where did the story come from?
The study was carried out by researchers from University College London, Imperial College London, Brighton and Sussex Medical School and London School of Hygiene and Tropical Medicine.
It was funded by the Multiple Sclerosis Trials Collaboration, University College London Biomedical Research Centres funding scheme, a number of registered charities and a personal contribution.
Most of the UK’s media reported the study accurately; however, The Independent’s headline – “Surprise discovery shows multiple sclerosis sufferers' lives are significantly improved by taking statins” – is misleading and inaccurate. The study was looking primarily at a patients’ brain size, not quality of life.
The effects of simvastatin on a patient’s quality of life are likely to remain uncertain until a phase III trial is carried out.
What kind of research was this?
This was an early stage (phase II) placebo-controlled randomised controlled trial (RCT), examining whether a cholesterol-lowering drug called simvastatin could help patients in the later stages of MS.
MS is a progressive disease, with many patients seeing a steady worsening of symptoms and disability.
An RCT is the best kind of study to determine the effectiveness of healthcare treatments. A phase II trial is usually designed to look at a treatment’s safety, how well it is tolerated and if it is worth testing in a larger (phase III) trial.
In its early stages, the disease is characterised by intermittent symptoms (called relapse-remitting MS), and some treatments have been developed that can reduce symptoms at this stage.
However, over 10-15 years, more than half of MS patients progress to a secondary stage (called secondary progressive MS), in which symptoms gradually worsen and there are fewer or no periods of remission.
MS occurs when a substance called myelin, which insulates the nerve fibres carrying messages to and from the brain, becomes damaged.
It is an autoimmune condition, which means the immune system mistakes the myelin for a foreign substance and attacks it.
The myelin becomes inflamed in small patches (called plaques or lesions), which can be seen on an MRI scan.
The researchers point out that in the secondary stages of MS, there is increasing brain atrophy (shrinkage). There are currently no treatments for the later stages of this disease.
They also say that statins have anti-inflammatory and other protective effects on the nervous system. An early trial of simvastatin in people with early stage MS showed a reduction in brain lesions, although other trials had conflicting results.
The purpose of this study was to see if simvastatin had a positive effect in a larger sample group with progressive MS.
What did the research involve?
The researchers set out to look at the potential effects of simvastatin in the secondary progressive stage of MS.
They randomly assigned 140 adults aged 18-65 with this stage of the disease to receive either a daily dose (80mg) of simvastatin or a placebo drug for two years.
All the patients, their doctors and the researchers assessing the trial outcomes were “masked” to treatment allocation.
This means they did not know whether patients were getting simvastatin or the placebo drug.
This type of double-blind testing is regarded as the “gold standard” of assessing the effectiveness of a drug or intervention.
The researchers were primarily interested in the effect of simvastatin on brain atrophy (or wastage). To measure this they took MRI scans of the patients’ brains at the start of the study and then again at 12 and 25 months. The last scan was undertaken one month after the last medication was taken. They based their calculations on an assumption that in this stage of the disease, the brain atrophies (shrinks) by about 0.6% a year.
They also used a number of disability scales at the start of treatment, and at 24 months, to look at whether simvastatin had any effect on patients’ disability. It also looked at the frequency of relapse in symptoms (a common problem with MS) compared to the placebo.
They also looked at levels of various markers in the blood linked to immune system function and inflammation.
The results were adjusted for factors such as sex and gender, and serious adverse effects were recorded.
What were the basic results?
Researchers found that the average rate of brain atrophy was 43% lower in patients in the simvastatin group (0.288% per year than in those in the placebo group – equivalent to 0.584% per year).
Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in the number of participants who had serious adverse events (20% in the placebo group and 13% in the simvastatin group).
A small but significant positive effect was seen on the patient-reported MS impact scale for people taking simvastatin. Overall symptoms were 4.47 points less, on a scale of 29 to 116.
Simvastatin also showed a similarly small but significant positive effect in one disability scale, but with no difference in another scale.
There was no effect seen on blood markers, rate of new and enlarging lesions, or the frequency of relapse.
How did the researchers interpret the results?
The researchers say that a daily 80mg simvastatin might be a treatment option for secondary progressive MS, although warrants further investigation. How simvastatin might help protect against brain atrophy is still unclear, but they believe it could be due to the effect on vascular function or cell protection.
This was an early stage, phase II trial, which found that simvastatin reduced the rate of brain shrinkage in patients in the later stages of MS.
The results are promising and warrant a larger phase III trial, examining whether the drug could slow the disease in patients at this stage of MS.
It should be noted that although simvastatin had some effect on outcomes in one disability scale and one symptom scale, the trial was primarily aimed at measuring the effect on brain shrinkage, rather than patients’ symptoms.
To conclude, it is unclear what effect simvastatin, if any, would have on long-term quality of life for MS patients.
A final interesting point is how simvastatin is actually reducing brain shrinkage. If we discovered the mechanisms involved, this could lead to new treatment strategies.