Commercial availability of a JC virus antibody assay will change practice in caring for patients with MS.

Patients with multiple sclerosis (MS) or Crohn disease who are taking natalizumab face an increased risk for progressive multifocal leukoencephalopathy (PML) if they have been exposed to JC virus, the FDA warned in January. The agency also announced approval of a new blood test to detect JC virus antibodies.

JC virus is common and usually harmless, the agency said, but its presence can be dangerous in patients taking immunomodulating drugs like natalizumab. Other risk factors associated with developing PML while on natalizumab are treatment with natalizumab for longer than 2 years and previous treatment with immunosuppressant drugs such as methotrexate or cyclophosphamide (but not prior use of first-line injectable immunomodulatory agents, interferon-beta, or glatiramer acetate).

The FDA estimates that patients with all three risk factors face about a 1% risk for PML with natalizumab therapy (11 cases per 1000 patients treated).

Natalizumab’s label will be changed to reflect the new information.

Comment: Commercial availability of a JC virus antibody assay will change practice in caring for patients with MS. The risk for PML with natalizumab was previously said to be about 1 in 1000, but recent safety data provided by the manufacturer indicate that the overall incidence of PML is more than double that (2.11 per 1000 as of February 2012). The major advance for patient safety is recognition that the PML risk can be stratified by three risk factors (treatment duration >2 years, prior immunosuppressant use, and JC virus antibody seropositivity). As highlighted by the FDA, in patients with all three risk factors, the risk for PML is very high (>1 in 100). On the other end of the spectrum, the PML risk with natalizumab appears to be quite low in patients who are JC virus–seronegative. For these patients, the manufacturer estimates the PML risk to be about 1 in 10,000, with a 95% confidence interval potentially as high as 1 in 2000 and as low as zero, based on the lack of observed PML cases in JC virus–seronegative patients to date and the false-negative rate of the assay (3%). The seroconversion rate for JC virus in MS patients is about 2% per year; the optimal frequency of testing for the virus in patients taking natalizumab remains to be defined. This is a fast-moving field, so further refinement of these numbers is likely as more safety data become available.

Source: Journal Watch Neurology