Anti-JC Virus Antibody Titer Changes during Natalizumab Treatment in a Swedish MS Cohort (P02.139) (2012)

Objective: To assess anti-JCV antibody titer changes in patients with Multiple Sclerosis (MS) prior to and after initiation of treatment with natalizumab. Background Progressive multifocal leukoencephalopathy (PML) is a known side effect associated with natalizumab. Recently, an analytically validated anti-JCV antibody assay has been introduced into clinical practice to stratify patients with MS for higher or lower risk of PML. Design/Methods: The anti-JCV antibody assay (Gorelik et al., Ann. Neurol. 2010) was applied to serum samples of Swedish MS patients during treatment with interferon beta (n=415), prior to (n=840), and during treatment with natalizumab (n=840). Positive samples were diluted in 1:3 dilution steps to determine titer levels. A randomly selected proportion (n=211) of the same patients were also tested for 1:3 dilution titers of antibodies toward a nuclear human-cytomegalovirus (CMV) antigen (Schmitz et al., J. Clin. Microbiol. 1977). In addition, 716 of the patients were studied for antibodies toward the recombinant varicella-zoster (VZV) glycoprotein E antigen (Thomsson, J. Virol. Methods 2011). Results: The majority of patients did not change in anti-JCV antibody titers during treatment with natalizumab. However, in anti-JCV antibody positive patients, the relative number of patients having a decrease in anti-JCV antibody titers was higher in natalizumab treated patients compared with interferon beta treated patients, suggesting an effect of natalizumab treatment on the humoral immune response to JCV. While this was not seen for titers toward CMV, anti-VZV-IgG antibodies also declined in a majority of the natalizumab treated patients. Whereas only 5% of all anti-JCV antibody positive patients during natalizumab treatment showed an increase in anti-JCV antibody titers, a Swedish PML case demonstrated rising titers prior to diagnosis - albeit only by one titer level compared with baseline. Conclusions: An increase in anti-JCV antibody titers during natalizumab therapy warrants further study in the context of PML risk stratification. Supported by: CW is supported by an ECTRIMS fellowship stipend. We acknowledge the help of A. Mattsson, E. Karlberg, M. Lundqvist, C. Hermanrud, H. Westerlind, R. Ramanujam, A. Ahlberg, R. Jungedal, J. Link, I. Lima Bomfim, B. Davoudi, V. Bedarova, L. Mascarell Maricic, A. Carlsson, M. Johansson and K. Fink to realize this project. Disclosure: Dr. Warnke has nothing to disclose. Dr. Subramanyam has received personal compensation for activities with Biogen Idec as an employee. Dr. Subramanyam holds stock and/or stock options in Biogen Idec. Dr. Bergstrom has nothing to disclose. Dr. Goelz has received personal compensation for activities with Biogen Idec and Elan Pharmaceuticals as an employee. Dr. Goelz holds stock and/or stock options in Biogen Idec., which sponsored research in which Dr. Goelz was involved as an investigator. Dr. Goelz holds stock and/or stock options in Biogen Idec. Dr. Goelz has received research support from Biogen Idec. Dr. Plavina has received personal compensation for activities with Biogen Idec as an employee.Dr. Plavina holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Plavina was involved as an investigator. Dr. Kockum has nothing to disclose. Dr. Rahbar has nothing to disclose. Dr. Olsson has nothing to disclose. Dr. Hillert has received personal compensation for activities with Biogen Idec, Merck-Serono, Novartis and Teva Neuroscience as participant on advisory boards, consulting and/or speaking engagements.Dr. Hillert has received research support from Sanofi-Aventis Pharmaceuticals, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec and Merck-Serono. Dr. Fogdell has received research support from Biogen Idec, Merck Serono, and Sanofi-Aventis Pharmaceuticals, Inc.