Risk Factors for Lymphopenia in Patients with Relapsing Remitting Multiple Sclerosis Treated with Dimethyl Fumarate
Objectives: To identify risk factors for (DMF-induced lymphopenia and characterize its impact on T lymphocyte subsets in MS patients.
Methods: We performed a retrospective analysis of 93 MS patients treated with DMF at BIDMC since 2013. We reviewed demographics, ethnic background, prior medication history, complete blood counts and T lymphocyte subsets. Possible lymphopenia risk factors examined include age, prior natalizumab exposure, vitamin D levels, and concomitant exposure to carbamazepine, opiates, tobacco, or steroids. Lymphopenia was define as grade 1: absolute lymphocytes count (ALC) 800-999/ul; grade 2: ALC 500–799/ul; grade 3: ALC 200-499/ul and grade 4: ALC <200/ul.
Results: MS patients were on DMF monotherapy for a median of 12 months (range 5-35). These included 84% Caucasians and 16% African Americans. Of 93 DMF-treated patients, 38 (40.8%) developed any grade of lymphopenia and reached an ALC nadir after a median of 486 days (range 82-889). Lymphopenic patients included 17 (18.2%) grade 1, 15 (16.1%) grade 2, and 6 (6.4%) grade 3 individuals. Compared to baseline levels, CD8+ T-cells were more reduced than CD4+ T-cells (84% versus 58% in patients with lymphopenia, p< 0.0004) and CD4/CD8 ratio increased from 2.0 to 4.0. In Caucasian patients, lymphopenia occurred in 44.8%, which is significantly elevated compared to 9% African-Americans (p<0.05). Risk of developing lymphopenia increased with concomitant steroid exposure (p<0.02). We observed a trend for increased incidence of lymphopenia in smokers, patients treated with carbamazepine, and those with normal vitamin D level (>30 ng/ml) at the time of lymphopenia. Prior exposure to natalizumab, age, BMI<25, or opiate use were not associated with the incidence of lymphopenia.
Conclusions: Lymphopenia occurs frequently in DMF-treated MS patients and affects CD8+ more than CD4+ T-cells. Caucasians and patients exposed to steroids had a higher incidence of lymphopenia. Further data analysis is in progress.