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Jeremy Chataway Interview, University College London, May 2014
Dr Jeremy Chataway MA, PhD, FRCP Consultant Neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, University College Foundation NHS Trust, London and at St Mary’s Hospital (Imperial College Healthcare NHS Trust) is interviewed. Dr Chataway led the randomized, placebo controlled Phase II MS-Stat Trial.
Q1: Secondary progressive MS accounts for most of the disability in patients with MS. So why are there not the same range of treatments available for progressive MS as for relapsing remitting MS?
Progressive MS is the second stage of MS, neurodegenerative, while the primary rrMS is inflammatory driven. The biology of the progressive MS is much less well understood and therefore there currently are less therapeutic options.
Q2: What exactly is simvastatin and what made you choose it for your study on secondary progressive MS patients?
Simvastatin is a very well-known drug that lowers cholesterol, and is effective in treating heart attacks and stroke. It also is involved with other molecules that have neuroprotective functions. A lot of animal work has been done as well as promising clinical studies with the molecule for treating rrMS. It also is a simple and safe molecule. For these reasons I decided to investigate the effects on progressive MS.
Q3: There has been a lot of recent controversy around the safety of statins. How safe do you consider it to be?
In the 140 people tested thus far it was completely safe, although we were ready for certain side effects. There was no difference from placebo, and this was a high dose (80 mg, where 40 is used to lower cholesterol) that was used. It is thus well tolerated.
Q4: What were the important features of this study’s design?
The study population was truly secondary progressive MS patients. They received either placebo or the drug, in a blinded fashion, and were followed for two years. MRI scans were taken at 0, 1 and 2 years. Also disability measurements were included, both from a patient’s and a clinician’s point of view. Finally, also safety was assessed.
Q5: What were the major results?
The atrophy rate (brain shrinkage) was the primary outcome of the study. The treatment group had only 43% of the brain shrinkage seen in the placebo group. This is important as brain shrinkage seems to be linked to the level of disability. Secondary outcomes: patient disability also seemed to be less in the treatment group.
Q6: The effect of statins in MS has been mixed prior reported research. Could you give us an overview of these results and tell us where your results fit it?
This has been the first trial in secondary progressive MS. Previous studies in rrMS did not show consistent results. These trials were probably not powerful enough, as it were add-on studies. Perhaps the statins do not work in the earlier phases, but it may thus also be an effect of study design.
Q7: What were the weaknesses of the study in your opinion?
It had a limited budget, as it was charity funded. With more budget we could have added more and fancier measurements and perhaps use different doses.
Q8: What is your proposed mechanism by which statins functioned to lead to these results?
There was no effect seen on immunological markers. Patients were over 50, and perhaps the more general vasculo-protective effect is strengthening the damaged vasculature. Also cholesterol levels were down in the treatment group, possibly leading to a better general health of these patients. But more research into the mechanism of action is required.
Q9: In light of this study’s results, what are your recommendations to patients and to MS specialists, ad what are your next steps?
This was a phase II study, so it is not an MS drug yet. But, clinicians may think of implementing statins in MS patients with high cholesterol, under careful monitoring conditions. In the phase III we will look primarily at disability, in 900-1000 patients, to be followed for about 3 years. There currently is no drug that shows an effect on disability in secondary progressive MS.