Factors associated with dimethyl fumarate-induced lymphopenia

J Neurol Sci. 2019 Mar 15;398:4-8. doi: 10.1016/j.jns.2019.01.007. Epub 2019 Jan 8.


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.

Keywords: Dimethyl fumarate; Lymphocyte subsets; Lymphopenia; Multiple sclerosis; Risk factors.

MeSH terms

  • Adult
  • Dimethyl Fumarate / adverse effects*
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Longitudinal Studies
  • Lymphocyte Count / methods
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism*
  • Lymphopenia / blood*
  • Lymphopenia / chemically induced*
  • Lymphopenia / diagnosis
  • Male
  • Middle Aged
  • Prospective Studies


  • Immunosuppressive Agents
  • Dimethyl Fumarate