Author Of 1 Presentation
P0371 - Practice improvement by retrospective analysis of changes in lymphocyte levels in patients with multiple sclerosis on dimethyl fumarate. (ID 394)
Abstract
Background
There are currently no recommendations on lymphocyte subset monitoring as best practice for patients on disease-modifying therapies, including dimethyl fumarate (DMF). Instead, patients are monitored for general lymphocyte count, which may mask changes in subsets of clinically relevant cell populations. There have been several cases of patients on DMF without severe lymphopenia but did have a high CD4+:CD8+ T cell ratio who went on to develop progressive multifocal leukoencephalopathy (PML), caused by the reactivation of John Cunningham virus (JCV). These incidents suggest that monitoring changes in subpopulations is clinically relevant and important. Since CD3+CD8+ (CD8+) T cells and CD3-CD56+ Natural Killer (NK) cells are primarily responsible for eliminating cells with actively replicating viruses., changes in circulating levels of these specific populations of cells may put patients at risk of developing recurring infections, including JCV.
Objectives
Our objective was to characterize the changes in immune profile associated with use of DMF. We hypothesized that CD4+ T cells counts would remain relatively stable while CD8+T cells and NK cell levels would decrease. Demonstrating changes in the relevant lymphocyte populations in our cohort will promote monitoring and assessment of lymphocyte subpopulations of patients on DMF.
Methods
A retrospective analysis of longitudinal data from 299 patients who have been treated with dimethyl fumarate at the Fraser Health Multiple Sclerosis clinic in British Columbia, Canada. The blood test results date range from January 1 2013- April 1 2020. The following cell populations were analysed: white blood cells, neutrophils, lymphocytes, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3+ cells, CD19+ B cells and CD3-CD56+ NK cells. We created a linear regression model to estimate average changes in lymphocyte subpopulation counts.
Results
On average, our patients remain on DMF for 31 months, after which time CD8+ T cell count decreases by -67% and reaching lower range after 21 months. CD4:CD8 T cell ratio increases 41.6% and reaches upper range only 2 months after treatment start. White blood cells, lymphocytes, CD4+ T cells and NK cells also decrease (-29%, -49%, -48% and -52%, respectively) but at a much slower rate. During recovery, while CD8+ T cells, CD4+ T cells, NK cells and lymphocytes were able to recover in 3-4 months, CD4:CD8 T cell ratio would not recover until 9 months after treatment end.
Conclusions
Our results suggest that lymphocyte count may not be sensitive enough to detect early and critical changes to lymphocyte subsets that may be important for preventing viral infection.