Many of you have commented on this blog and sent emails asking about the results of a trial we conducted a number of years ago to test simvastatin (brand name Zocor) as a treatment for vitiligo. I couldn’t comment on the results of the trial until it was reviewed and published, but this has finally happened and I’m happy to discuss the trial and its results here.
We first became interested in testing simvastatin after some observations we initially made in mice that get vitiligo. By studying vitiligo in both mice and my vitiligo patients, we discovered that a protein called interferon gamma, abbreviated IFN-g, is largely responsible for causing the disease to progress in the skin. This was an important observation, because it is largely responsible for our later studies to test a number of different treatments that turn off the effects of IFN-g. We have now found that many of these treatments work really well in the mice, and two have now been tested in humans, Xeljanz (tofacitinib) and Jakafi (ruxolitinib). Multiple pharmaceutical companies are interested in this pathway, and are working to develop new drugs for vitiligo and other autoimmune skin diseases.
Before we became aware of these new types of treatments, we were hopeful that existing, safe, and cheaper ones might be able to turn off IFN-g and treat vitiligo. I read in a few studies that simvastatin, and possibly other cholesterol lowering medications, could prevent some effects that IFN-g causes in cells grown in a dish. Then I read about a patient who took a medication for cholesterol and his vitiligo improved. Then I saw an email from a patient in Africa who has lost all of her color from vitiligo, but it started coming back after taking a cholesterol lowering medication (she wasn’t happy about this – she had become used to being one color). This was exciting, because simvastatin was available as a generic, was relatively safe, and very inexpensive.
So based on this information, we tested simvastatin as a treatment in our mice with vitiligo. We had to give a high dose of the drug to the mice, more than we would in a human, because mice increase production of the protein that the drug blocks when you treat them. So in order to test the drug, large doses have to be given to overcome this. In any case, these large doses worked in the mice, both preventing vitiligo and reversing it after it had appeared. We hoped it would be effective in humans as well. Merck, the company that produced simvastatin, was not interested in funding the trial, and wouldn’t even give us free medication to test. This was likely because simvastatin was available as a generic medication, and so they probably wouldn’t benefit from an expensive trial even if it worked. But because it was inexpensive as a generic (about $0.12 per pill) and my institution, the University of Massachusetts Medical School, was willing to fund the trial, we were able to recruit a small number of vitiligo patients to test it.
We decided to test the highest approved dose of the medication (80mg per day), because if it didn’t work we would have regretted not having tested the highest possible dose. However the Federal Drug Administration (FDA) had some concerns about this dose, because about 1:100 patients who take this dose complain of muscle pains, and a small number have severe muscle damage. Thus, we had to carefully develop a plan for the trial in collaboration with the FDA to reduce the likelihood of these side effects. So we only enrolled men in the trial, because women were more likely to have side effects from the drug. We also had to exclude patients with other types of diseases, and had to check blood tests every month.
Despite all of these limitations, we enrolled 15 patients in the trial – 7 were randomized to the placebo pill and 8 to simvastatin. Three of the simvastatin-treated patients withdrew from the trial, but only 1 from a symptom likely related to the treatment (vertigo, or dizziness). So 7 patients who took placebo completed the trial and 5 who took simvastatin completed the trial. Overall, we did not see improvement of disease in the simvastatin group compared to the placebo group, and so our trial does not support using this treatment for vitiligo patients. One patient in the simvastatin group had severe spreading of his vitiligo during the trial, but then had significant improvement before the end of the trial, all while taking the drug. We don’t know whether the drug caused the worsening of his disease, helped to improve it, or had no effect.
We wondered whether the trial was ineffective because we didn’t enroll the right patients. But one patient who was in the trial, received simvastatin, and didn’t improve, later came to my clinic, started nbUVB phototherapy, and is now MUCH better. So this told me that we had at least one patient in the trial who could respond to treatment but didn’t get better with simvastatin. So why didn’t it work in our trial, after we saw improvement in the mice? First, the effect in the mice was not nearly as strong as we have now seen with newer treatments that are coming for vitiligo. Second, the dose we had to use in the mice was very high, and we couldn’t safely use this dose in humans.
So we think that we are unable to test a dose that would be effective in humans due to its effect on the muscles. That said, another trial in Nice, France is currently testing a different cholesterol-lowering medicine, atorvastatin, as a treatment for vitiligo. This trial is being done by my friend, Dr. Thierry Passeron, and I’ll let you know when the results are available, particularly if they are positive. We also don’t know if maybe the treatment would work under different circumstances, such as if it were used as a topical cream (where a high dose could be achieved in the skin safely) or in combination with light therapy. But for now, don’t scramble to get simvastatin for your vitiligo. There’s always a chance that it will work in some people, and we just haven’t figured out exactly who that is yet. So if you’re already taking these drugs for other reasons, maybe it’s helping your vitiligo at least a little bit!