Image Source: UNI-MUENSTER
The multiple sclerosis treatment Tysabri (natalizumab) may be associated with increased levels of John Cunningham virus antibodies, indicating increased risk for fatal brain disease caused by the infection, according to recent data.
“There has been strong debate about whether the underlying [John Cunningham virus (JCV)] seroconversion rate by aging is influenced by treatment with natalizumab,” Heinz Wiendl, MD, of the University of Muenster, Germany, and colleagues wrote. “The high seroconversion, which has already been suggested, and the data of seroconversion rates in longitudinally monitored JCV patients in our study clearly support the facilitation by treatment with natalizumab.”
To identify a relationship between JCV infection and the immunosuppressant treatment, Wiendl and colleagues examined serum samples from patient groups in Germany (n = 1,921) and France (n = 1,259), as well as within a German subcohort followed for 15 months (n = 525) and a French subcohort followed for 24 months (n = 711). All patients were diagnosed with relapsing-remitting multiple sclerosis (MS) and were undergoing natalizumab therapy. Sera were analyzed using second-generation ELISA to determine incidence and changes in JCV serostatus and index value, the level of anti-JCV antibodies, among these cohorts.
Overall, JCV seroprevalence was 54.7% among the larger German cohort and 59% among the French cohort. Among patients observed longitudinally, serostatus changes from negative to positive occurred among 12.7% of the German cohort (10.3% per year) and 16.9% of the French cohort (8.5% per year).
Testing of JCV index values found the measure to be largely reproducible (R2 = 0.89), although 16% of the 50 retested serums saw a relevant discrepancy. When applying JCV index value analysis to a 201-person longitudinal cohort, anti-JCV antibodies rose during the study (P = .009), a change that the researchers wrote was not driven by aging. Taken together, the data suggest that treatment with natalizumab was associated in an annual anti-JCV antibody increase of 12.9%.
“Natalizumab did appear to increase the levels of anti-JCV antibodies and this higher level may be associated with a higher risk of [progressive multifocal leukoencephalopathy (PML)],” Wiendl said in a press release. “The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”
In a related editorial, Adil Javed, MD, PhD, and Anthony T. Reder, MD, both of the University of Chicago, wrote that the increased risk for PML is noteworthy, but still an unlikely outcome when compared with the more immediate impact of MS.
“The risk of PML in JCV-positive, natalizumab-treated patients without prior immunosuppressant therapy is 1:1,000 per year; the risk of an MS attack in untreated patients is one in two per year,” they wrote. “Despite a higher JCV replication state, an increase in [JCV antibody] index does not necessarily mean that PML infection is imminent.” – by Dave Muoio
Disclosure: Please see the full study and editorial for a list of the authors’ relevant financial disclosures.
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