FDA Issues Health Advisory for Raptiva

The FDA has issued a public health advisory following the deaths of three patients using the psoriasis drug efalizumab, which is marketed as Raptiva.

The agency said in its Feb. 19th advisory that there have been three confirmed reports -- and one possible case -- of progressive multifocal leukoencephalopathy, or PML, in adults using the drug since it was approved in 2003. All four patients, who ranged in age from 47 to 73, had been treated with efalizumab for more than three years; none of them had received other treatments that suppress the immune system while taking the drug.

Three of the patients -- two with confirmed PML and one with possible PML -- died.

The FDA announced in mid-October that it was requiring labeling changes, including a boxed warning, to highlight the risks of life-threatening infections, such as PML, associated with the use of efalizumab. At that time, the FDA directed Genentech, which manufactures efalizumab, to develop a risk evaluation and mitigation strategy for the drug that would include a medication guide to educate patients about the drug's risks.

The agency said in its February 19th advisory that it is reviewing this latest information and will take steps to "ensure that the risks of Raptiva do not outweigh its benefits, that patients prescribed Raptiva are clearly informed of the signs and symptoms of PML, and that health care professionals carefully monitor patients for the possible development of PML."

Efalizumab is a weekly injection approved for adults with moderate to severe plaque psoriasis. The drug suppresses a patient's immune system to reduce psoriasis flare-ups. However, suppressing the body's defense system can increase the risk of serious infections.

An opportunistic infection caused by the JC virus (so-named for the patient, John Cunningham, in whom it was first isolated) or PML affects the central nervous system in immunosuppressed people, leading to an irreversible decline in neurologic function and death. The FDA advisory said there is no known effective preventive measure or treatment for PML, and there is no laboratory screening test for the disease.

The FDA strongly recommends that physicians monitor patients on efalizumab -- as well as those who have discontinued the drug -- for any symptoms of neurologic disease, including unusual weakness, loss of coordination, changes in vision, difficulty speaking and personality changes. Use of efalizumab should be discontinued if PML is suspected.

The agency said physicians should be aware that efalizumab not only increases the risk of PML, but that long-term, continuous use may further boost this risk. Patients treated with efalizumab should be periodically re-evaluated to ensure that the benefit of treatment outweighs the risks, and consideration should be given to use of other approved therapies for plaque psoriasis.

Four other biologic agents have been approved for treatment of psoriasis:

Other approved treatments include ultraviolet light therapy; various topical agents; and the systemic drugs cyclosporine, sold as Neoral; acitretin, sold as Soriatane; and methotrexate, sold as Rheumatrex and Trexall.

The FDA said in its October news release that patients should receive all their age-appropriate vaccinations before starting treatment with efalizumab. Vaccinations should not be administered to patients taking the drug because immunity to the pathogen targeted by the vaccine may not be conferred.

In addition to symptoms of PML (e.g., confusion, dizziness, difficulty talking or walking, vision problems), patients taking efalizumab should be educated on how to recognize symptoms of anemia (e.g., dizziness on standing, weakness, jaundice), thrombocytopenia (e.g., bruising, bleeding gums, petechiae), or a worsening of their psoriasis or arthritis.

Physicians should inform patients about all the risks associated with efalizumab use and instruct them to seek immediate medical attention if they experience any of these symptoms.

Physicians and consumers may report serious adverse events associated with the use of efalizumab to MedWatch, the FDA's Safety Information and Adverse Event Reporting program, online or by calling (800) FDA-1088.