JC Virus Antibody Seropositivity Index Decreases with Reduced Infusion Frequency in Natalizumab-Treated Multiple Sclerosis Patients

Background: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system (CNS) that can occur in JC virus (JCV) antibody seropositive patients with multiple sclerosis (MS) treated with natalizumab. Atrisk patients are screened for the presence of JCV antibodies at 4-6 month intervals utilizing an index based assay (Focus Labs, CA). High or rising indices are associated with greater risk of PML, which could possibly be reduced by extending natalizumab infusion intervals from 4 to 8 weeks, and conceivably reflected in lower JCV antibody seropositivity index. 

Objectives: To determine whether if there is a statistically significant change in serum JCV antibody indices in natalizumab treated MS patients when extending the infusion frequency from 4 to 8 weeks.

Methods: We retrospectively reviewed 509 charts dated April 2011 to September 2015 of natalizumab treated MS patients aged 18-80 at Rush University Multiple Sclerosis Center. Data were analyzed via a paired t test.

Results: Sixty one patients were included in the study.  Excluded were patients without recorded JCV indices, under the age of 18, had not changed frequency of natalizumab infusions, or developed PML.  The median number of days between the baseline JCV antibody index value and the first followup observation after natalizumab infusion frequency changed to every 8 weeks was 178, and between the first and last observation at extended intervals was 330.  The mean baseline JCV index value was 2.2 (1.09 sd), at first follow-up observation 2.11 (sd 1.1), and 1.8 at last observation (1.01 sd). The change in JCV index value from baseline to first observation was not significant (mean change [sd]= -0.1 [0.6], p=0.2), but decreased significantly from baseline to last observation (mean change[sd]=-0.35 [0.59], p=0.0001) after patients received natalizumab every 8 weeks.

Conclusions: This study suggests that decreasing the frequency of natalizumab infusions from every 4 to every 8 weeks results in a significant decrease in the JCV antibody index value, which may indicate a lower the risk of developing PML. Further study is warranted to determine the significance of this observation.