The drug labeling of natalizumab (Tysabri), an immunosuppressant used in the treatment of relapsing forms of multiple sclerosis and moderate-to-severe Crohn's disease, has been revised for the third time in three years. Previously, there was a warning that the drug could increase the risk of progressive multifocal leukoencephalopathy (PML), a rare, fatal brain infection in which the myelin coating of nerve fibers is damaged. A newly identified risk factor for PML, the presence of anti–John Cunningham virus (JCV) antibodies, has now been added to the drug label's warnings. The name JCV actually refers to a family of common polyomaviruses infecting the majority of adults. It normally remains dormant in the body of an otherwise healthy person and doesn't create any significant health problems. However, patients with weakened immune systems have an increased risk of PML related to JCV.
The presence of anti-JCV antibodies is determined using a newly approved blood test, the Stratify JCV Antibody ELISA [enzyme-linked immunosorbent assay]. This test should be used as part of the determination of whether the risk of PML outweighs the benefit of natalizumab therapy in a particular patient. However, it can't be used as the sole means of determining one's risk of PML; there are two other known risk factors for PML in patients taking natalizumab: a long duration of treatment with natalizumab (especially longer than two years) and prior treatment with an immunosuppressant, such as mitoxantrone (Novantrone), azathioprine (Azasan, Imuran), methotrexate (Rheumatrex, Trexall), cyclophosphamide (Cytoxan), or mycophenolate mofetil (Myfortic). In patients with all three risk factors, it's estimated that 1.1% (11 out of 1,000) will develop PML. Patients who test negative for anti-JCV antibodies are still at risk for PML because they might acquire a JCV infection in the future or their laboratory result might have been a false negative. This means they may need to be retested during treatment to confirm that they remain antibody negative. Nurses should be aware of the risk factors for PML in patients receiving natalizumab and should work collaboratively to determine the patient's current anti-JCV antibody status.
PML has also been reported with use of brentuximab vedotin (Adcetris), an intravenously administered monoclonal antibody used to treat lymphoma. A boxed warning has been added to the label. Three cases of PML in patients receiving brentuximab vedotin have been reported to the Food and Drug Administration (FDA); one was noted at the time of drug approval in August 2011, and two more were noted between the time of approval and January 13 of this year, prompting the newer warning. Additionally, the label for brentuximab vedotin was revised to include a new contraindication: it shouldn't be used concurrently with the cancer drug bleomycin because of an elevated risk of pulmonary toxicity.
To read the FDA Drug Safety Communication regarding natalizumab, go to http://1.usa.gov/ys2YrU. The FDA Drug Safety Communication regarding brentuximab vedotin can be found at http://1.usa.gov/Ad83hK.