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Factors associated with dimethyl fumarate-induced lymphopenia
Susana Sainz de la Maza1, Silvia Medina2, Noelia Villarrubia2
1Department of Neurology, IRYCIS, REEM, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Background:
Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy.
Objective:
To identify factors associated with lymphopenia in DMF-treated patients and explore changes in blood lymphocyte subsets associated with DMF-induced lymphopenia.
Methods:
Prospective longitudinal study including 106 patients initiating DMF treatment followed for a median time of 24.67 months. Blood lymphocyte subsets were studied in 64 patients by flow cytometry at baseline and 6 months after.
Results:
Mean absolute lymphocyte counts (ALCs) decreased by 29% during the first year of DMF-treatment. Patients developing lymphopenia showed a faster decline within the three first months. A reduction of ALCs higher than 38% at this time was associated to subsequent development of grade 2-3 lymphopenia (OR = 5.93, 95% CI: 1.9-18.6, p = 0.002). All patients showed a significant decrease in different T and B lymphocyte subsets upon DMF therapy. In addition, lymphopenic patients experienced a selective decrease in natural killer T (NKT) cell percentages (p = 0.01), and a high drop in NKT total counts (p < 0.0001).
Conclusions:
Patients who experience a drop in ALCs by >38% at three months of DMF-treatment are about 6-times more likely to develop significant lymphopenia. This decrease is clearly associated with a considerable loss of NKT cells.
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