Brain Atrophy was chosen as the primary outcome in this study. This means that changes in the size or volume of the entire brain as measured on MRI scans at yearly intervals were used to determine if there was a difference between the 70 patients treated with Simvastatin and the 70 patients treated with placebo. This outcome was justified based on prior studies showing a relationship between the development of brain atrophy and the development of worsening disability in MS patients. By using brain atrophy as the primary outcome the study investigators were able to observe a treatment effect of simvastatin with fewer study patients and a shorter study time interval. In contrast a study to determine if simvastatin reduced the development of sustained disability in MS would require many hundreds of patients potentially for a longer interval. Interestingly, the investigators did report a possible benefit on two clinical disability measures at 2 years, though the significance of this benefit is unclear at this time.
These are very hopeful preliminary results but caution must be advised until further studies are completed for the following reasons:
- Statin therapy has already been studied in early relapsing forms of MS with mixed results
- Statin therapy can have significant adverse effects in some patients although no significant problems were observed in this study
- This is a phase II study in a relatively small number of patients (140 to be exact) and must be confirmed in a later phase III study; it is not unusual for a phase III study to show negative results even though a prior phase II study was positive
- The mechanism of benefit from high dose statin therapy is unclear and this could guide us in the selection of the most appropriate patients for this therapy. For instance, there does not appear to be a significant effect on relapses or new MRI lesions. Therefore, is the drug neuroprotective or is it having an effect on vascular comorbidity (a known benefit of statins) that is indirectly limiting brain atrophy in some patients?
- We do not know if the reduction in atrophy is affecting the white matter or the gray matter from the published study results. A reduction in gray matter atrophy would be far more compelling, since gray matter atrophy seems to the main driver of disability in MS
So what should you do with these results if you have secondary progressive MS? After all, the simvastatin was well tolerated in this group of patients. I suggest talking it over with your physician and certainly consider this drug and dosing schedule if you require statin therapy to lower cholesterol or if you have other accepted cardiovascular or cerebrovascular risk factors known to be benefited by statin therapy. I would also encourage you to participate in any Phase III trials of statin therapy that you may hear about in the coming months