I. Concerns About Elidel and Protopic and Cancer
Several years ago the Food and Drug Administration (FDA) required that a warning about cancer risk be added to the package inserts for Elidel and Protopic (E/P). This issue has been extensively reported in the popular press. We have carefully reviewed all the available information (including the information on which the FDA recommendation is based) and the FDA’s rationale for its recommendation. Subsequently, we have continued to monitor information as it became available.
E/P are members of a class of drugs that are potent suppressors of the immune system. This class of drugs has been used for many years to prevent organ transplant rejection. When injected or taken orally, these drugs increase cancer risk in a predictable way. The higher the dose, the greater the risk. (When applied to the skin, entry into the body circulation is poor and very little of the drug enters the blood stream.) The way this works is well understood and the increased risk is for particular kinds of cancer, not for cancer in general. It is possible, by examining cells from a cancer, to tell if the cancer was related to the immunosuppressive effects of the drug or not.
Because E/P are so effective for eczema they have been widely used since they came to market. Several million people have used Elidel, Protopic or both. Because having eczema doesn’t protect one from other diseases, we expect that some people using E/P will develop diseases that people get such as diabetes, heart disease, arthritis, multiple sclerosis and cancer: they would have gotten these diseases anyway.
Twenty-nine cases of cancer in patients using E/P were included in the initial report. These cases have been critically reviewed by cancer experts. We have examined those reviews. None of the cancer cases are similar to the kinds of cancer that has been seen in patients receiving high doses of this family of drugs by the oral or IV route. Over the years since the warning there has been no increase in the types of cancer related to E/P. The possible risk is still there but we believe, based on the reviews of the information available, that there is no evidence, at this time, that E/P has caused cancer.
Elidel and Protopic have been like a miracle for some patients. We carefully consider the risks and benefits of all treatments for our patients. We do not recommend discontinuing E/P. Parents, however, are the ultimate decision-makers for their children.
II. Advair and Serevent Questions
There have been reports in the news media of increased risks of asthma deaths in patients receiving Serevent. Because Advair contains Serevent, Advair is included in the media reports. These reports are based on information from the SMART Study, a safety study of Serevent that was active from 1996 to 2000. We participated in the SMART study and are very familiar with those results. We are also familiar with the FDA position and expert commentaries. In the SMART Study, patients receive their usual asthma medications and either Serevent or placebo (non-active inhaler). Patient monitoring in this study was limited. An interim analysis of the study data on 25,858 patients showed the following:
Among Caucasian patients (71% of the group) there were no differences in the Serevent and placebo groups.
Among the African American patients (17% of the group) there was a slight, but significant, increase in asthma related events in the Serevent group compared to the placebo group.
The African American patients in this study were less likely to be using inhaled steroids than the Caucasian patients. Only about 1/3 of these patients were using inhaled steroids despite the fact that the African American patients had more severe asthma than the Caucasian patients.
Advair and Serevent have been studied and used for many years. There have been 24 million patient years experience with Serevent and more than 20 million patient years with Advair. We know a lot about these drugs.
Advair and Serevent have been shown to be safe in many studies.
Serevent is not a good choice as the only drug for persistent asthma. It works very well with inhaled steroids (Flovent, Beclovent, Azmacort and probably Pulmicort).
Serevent improves outcomes for patients treated with inhaled steroids (2002 National Asthma Guideline revision) and allows the use of a lower dose of inhaled steroids. The excellent results when combining Serevent with an inhaled steroid led to the development of Advair.
We are currently participating in a study of African-American asthma patients comparing Advair with Flovent (an inhaled steroid) alone.
Because of the outstanding benefits of Advair for patients with asthma and because the current information does not raise safety concerns about the combination of Serevent and inhaled steroid (such as in Advair), we continue to prescribe and recommend Advair for our patients.