A single antibody measurement of viral activity for the JC virus may not be sufficient to assess risk for the often fatal disease progressive multifocal leukoencephalopathy (PML) in patients receiving immunomodulatory therapies that have been shown to reactivate the virus, according to a research note published online June 6 in the New England Journal of Medicine. Given the finding that one-third of multiple sclerosis (MS) patients had viremia but tested seronegative suggests a more comprehensive risk-mitigation strategy involving periodic monitoring over the course of natalizumab treatment may be necessary, say the authors. Plasma samples from separate cohorts of MS patients who received monthly infusions of natalizumab were analyzed for the presence of JC virus antibodies and viral DNA. Blood samples were obtained at baseline before the first infusion (n=26) and for several months during the first year of treatment as well as blood samples after more than 24 months of treatment (n=23). The researchers found that more than one-third (17 of 49 patients) had viremia at some point during the study. Viremia was present in 10 of 26 patients in whom treatment was initiated, including four who were seronegative (antibody titer, <2560) and six who were seropositive (antibody titer, ≥2560). […]
A single antibody measurement of viral activity for the JC virus may not be sufficient to assess risk for the often fatal disease progressive multifocal leukoencephalopathy (PML) in patients receiving immunomodulatory therapies that have been shown to reactivate the virus, according to a research note published online June 6 in the New England Journal of Medicine. Given the finding that one-third of multiple sclerosis (MS) patients had viremia but tested seronegative suggests a more comprehensive risk-mitigation strategy involving periodic monitoring over the course of natalizumab treatment may be necessary, say the authors.
Plasma samples from separate cohorts of MS patients who received monthly infusions of natalizumab were analyzed for the presence of JC virus antibodies and viral DNA. Blood samples were obtained at baseline before the first infusion (n=26) and for several months during the first year of treatment as well as blood samples after more than 24 months of treatment (n=23). The researchers found that more than one-third (17 of 49 patients) had viremia at some point during the study. Viremia was present in 10 of 26 patients in whom treatment was initiated, including four who were seronegative (antibody titer, <2560) and six who were seropositive (antibody titer, ≥2560). Of these 10 patients, viremia was present at baseline in four and three were seropositive. Of patients who received more than 24 infusions, seven of 23 had viremia and two were seronegative. For comparison, blood samples from 18 healthy volunteers demonstrated that six were seronegative, 12 were seropositive, and none had detectable viral DNA.
“The relatively high percentage of patients who had viremia and were seronegative appears to be greater than the false negative rate identified previously,” write the authors, led by Eugene Major, Ph.D., from the National Institute of Neurological Disorders and Stroke in Bethesda, Md. “To establish risk-stratification algorithms for PML in patients who receive potent immunomodulatory therapies, a single measurement of viral activity such as a test for antibodies to JC virus may be useful, but not sufficient to assess risk.”
