Clinical trials of natalizumab identified an elevated risk of PML, which causes progressive and often irreversible neurodegeneration, in patients taking the medication. As of January 4, 2012, 201 cases of PML have been identified in 96582 patients treated with natalizumab. Although PML is a rare adverse event, it is particularly concerning because JCV infection is common; it is usually harmless in individuals who are not immunocompromised but can be deadly and difficult to treat in patients who are immunocompromised as a result of a medical condition or treatment with an immunomodulating drug such as natalizumab. A mandatory registry program was created for patients taking the drug in 2006 to help the FDA and the drug’s maker better assess the risk.
Now evidence is emerging that may help physicians better assess an individual patient’s risk of developing PML. In addition to testing positive for anti-JCV antibodies, prior treatment with an immunosuppressing drug and longer-term treatment (particularly longer than 2 years) with natalizumab are factors that are associated with elevated risk, the FDA alert said. Among patients who have all 3 risk factors, the risk of developing PML is 11 in 1000.
More information about the risk levels of individuals with various combinations of these risk factors are available at the FDA’s website.
“The risks and benefits of continuing treatment with Tysabri should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more additional risk factors,” advised the FDA.