Botox, Psoriasis, and drug safety
Physician do no harm. This simple statement is the crux of medical therapy, but it can be complicated to weigh the risk/benefit ratio of many treatments. Too much aspirin causes tinnitus (ringing ears) and bleeding stomach ulcers, yet low dose aspirin is a nearly ubiquitous recommendation as a way to reduce the risk of heart attacks and stroke. More problematic is when a drug is shown to cause unexpected side effects. This was the case with Raptiva, or efalizumab, a medication used to treat psoriasis. Raptiva was pulled from the market June 8 after 3 cases of a deadly brain infection called progressive multifocal leukoencelphalopaty (PML) occured in 1,900 patients who had received the drug for more then 3 years. I was sad to see Raptive go, because it was a life-changing drug for many of my patients who were using it, but there was no way I would have continued prescribing it anyway; we had already contacted our patients on the drug and begun transitioning them to something new before the drug was pulled. Genentech, the maker of Raptive, pulled the drug from the market voluntarily, and had maintained a running dialogue as the problem unfolded, so they were in no way the evil corporation out for profit above safety. What this does show, however, is the difficulty in finding rare side effects that occur only after prolonged use. Certainly we should all look at any new drug askance while experience with it accumulates, but when the disease is severe and options are limited, sometimes the benefits outweigh the unknown risks.
On a different note, recently Botox received a dreaded “black box” warning label from the FDA. Black box warnings are given to drugs with potentially fatal side effects, but this is another example of the FDA using a broad brush to deal with an unlikely problem. Botox is based on a protein, botulinum toxin type A, produced by a bacteria called Clostridium botulinum. The protein prevents muscles from contracting. A person who eats a damaged can of food that has been contaminated with Clostridium botulinum will lose muscle control and be unable to breath. When using this protein as Botox, the dose that will be fatal to 50% of adults is about 3,000 units. When I inject Botox, however, the maximum dose needed is 100 units and most people receive between 25 and 50 units. That is a broad margin of safety, equal to or greater then most drugs including aspirin. So what is the problem? Botox is also used to relieve the painful muscle spasms of children with cerebral palsy, and the dose used is much larger. In that group there have been problems with generalized muscle weakness. To date, I have never read of a documented serious side effect from Botox used for cosmetic purposes, and I have never had one in my practice. This then is an example of the FDA lumping instead of splitting; the black box warning should have been limited to the medical use of Botox and reflected the risk from using large doses.
Separately, there is a competitor to Botox finally approved by the FDA for use in the United States: Dysport. I am glad Botox finally has some competition, which should slow down price increases on this already very expensive drug. Dysport and Botox have been used in Europe for 17 years, however, and yet Botox has 90% of the market share overseas. The reason is the difference in the protein itself; botulinum toxin type A is a biologic drug, produced in factories by culturing Clostridium botulinum, and the two drugs use different strains. Accordingly the two drugs are different in potency and effect; Dysport is more likely to spread further from the point of injection, which is not good for the small areas we treat on the face. I don’t intend to use Dysport anytime soon, except for the armpits where I use it to treat excessive sweating (hyperhidrosis) and the increased spread of the medication would be a good thing. Still, I hope Dysport achieves enough market share to keep the makers of Botox honest about pricing.