LB06
Longitudinal Changes in JCV Titers in Multiple Sclerosis (MS) Patients Treated with Rituximab, Fingolimod, and Dimethyl Fumarate
Progressive Multifocal Leukoencephalopathy (PML), a potentially fatal demyelinating disease caused by the John Cunningham virus (JCV), has occurred as a complication of treatment with rituximab, fingolimod and dimethyl fumarate. A positive JC titer indicates exposure to JCV and potential risk for PML.
Objectives:
The primary objective of this study was to determine changes in JC antibody titers in MS patients treated with rituximab, fingolimod and dimethyl fumarate: Secondary objectives included determination of any relationship between total lymphocyte count and patient characteristics with JC titers.
Methods:
Retrospective chart review of 172 patients (fingolimod 46, rituximab 22, dimethyl fumarate 104) treated at the Winthrop Comprehensive MS Care Center from January 1, 2013 to September 1, 2016 with JC titers known before starting the medication and then obtained on an ad hoc basis.
The initial analyzed JC value was obtained at most 6 months before treatment was started. The titers were evaluated for change during the course of therapy.
Serostatus change, defined as change in titer interpretation from one category to another: Negative (<.2), Indeterminate (.21- .4) or positive (>.4) during the study, was recorded.
All analyses were done using SAS 9.4® with p-values ≤ 0.05 being statistically significant.
Results:
JC Index titer: There was a significant decrease in JC titer index in patients treated with rituximab (p = 0.013). A non-significant decreasing linear trend in JC titer index occurred in patients treated with dimethyl fumarate (p = 0.752) and fingolimod (p = 0.321).
Lymphocytes: A significant linear decrease in lymphocyte count for dimethyl fumarate (p <.001)) and fingolimod (p = 0.014) occurred. A significant linear increase in lymphocyte count occurred with rituximab (p = 0.008). There was no association with lymphocyte count and JC titer for any medication.
Conclusions:
JC index titers significantly decreased in MS patients treated with rituximab, and show a non-significant decease for fingolimod and dimethyl fumarate. It is possible that rituximab impaired the serologic immune response to the JC virus. A declining JC titer in rituximab treated MS patients should not necessarily be interpreted that the risk of PML is also declining.