ORLANDO—In anti-JCV antibody–positive natalizumab-treated patients with multiple sclerosis (MS) and no prior immunosuppressant (IS) use, a higher anti-JCV antibody index correlates with an increased risk of progressive multifocal leukoencephalopathy (PML), according to research presented at the Fifth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).
Tatiana Plavina, PhD, Meena Subramanyam, PhD, and colleagues from Biogen Idec, Inc, examined the association between anti-JCV antibody index (anti-JCV antibody level as measured using the STRATIFY JCV DxSelect assay [Focus Diagnostics, Cypress, California]) and PML risk in anti-JCV–positive patients enrolled in natalizumab clinical studies and from postmarketing settings. Anti-JCV antibody index data were available from 71 natalizumab-treated PML patients at least six months prior to PML diagnosis and from 2,522 non-PML anti-JCV antibody–positive patients.
Low Index, Lower Risk
In cross-sectional analyses, anti-JCV antibody index was not associated with duration of natalizumab treatment (less than or equal to 24 versus more than 24 infusions) or prior IS use but was significantly associated with PML risk. A different relationship was observed between anti-JCV antibody index and PML by prior IS use. Hence, the association between anti-JCV antibody index and PML risk was assessed using all available longitudinal data in anti-JCV–positive patients without prior IS use, and estimated odds ratios across a range of thresholds of interest varied from 7 to 23 for the occurrence of PML at higher versus lower index.
According to previous work by Bloomgren et al, risk of PML in natalizumab-treated anti-JCV antibody–negative patients with MS is less than or equal to 0.1/1000. Anti-JCV antibody–positive patients with no prior IS use who have low anti-JCV antibody index may have severalfold lower PML risk, compared with current risk estimates assigned to all anti-JCV antibody–positive patients with no prior IS use as per the current algorithm. The researchers concluded that “anti-JCV antibody index may further differentiate PML risk for natalizumab-treated anti-JCV antibody–positive MS patients with no prior IS use.”
Stability of the Index Over Time
The researchers also looked at the longitudinal stability of the anti-JCV antibody index. In the AFFIRM and STRATIFY-1 study cohorts, of those patients who tested anti-JCV antibody-negative at baseline, 87% remained consistently negative and 96% remained consistently at lower risk (anti-JCV antibody index less than or equal to 0.9, 1.2, or 1.5) for a period of 18 months, with testing every six months. “These analyses may potentially better inform PML risk in patients who seroconvert or test intermittently positive,” the researchers said. Further, the investigators noted that 96% of natalizumab-treated patients who developed PML and had two or more samples available (n = 25) had pre-PML samples with an index consistently above 0.9.
—Glenn S. Williams
Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012;366(20):1870-1880.
Lee P Plavina T, Castro A, et al. A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol. 2013;57(2):141-146.
Plavina T, Berman M, Njenga M, et al. Multi-site analytical validation of an assay to detect anti-JCV antibodies in human serum and plasma.