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Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance

Erin E Longbrake1, Robert T Naismith2, Becky J Parks2

  • 1Washington University in St. Louis, Department of Neurology, 660 S. Euclid Ave., Campus Box 8111, St. Louis, MO 63110, USA.

Multiple Sclerosis Journal - Experimental, Translational and Clinical
|November 10, 2015
PubMed
Abstract

Insights

Dimethyl fumarate (DMF) can cause lymphopenia in multiple sclerosis (MS) patients. This condition, particularly when severe, may not resolve and warrants monitoring, especially in older patients or those switching from natalizumab.

Area of Science:

  • Neurology
  • Immunology
  • Pharmacology

Background:

  • Dimethyl fumarate (DMF) is a disease-modifying therapy for multiple sclerosis (MS).
  • DMF can induce lymphopenia, a decrease in lymphocyte count, in some patients.
  • The clinical implications of DMF-induced lymphopenia, including potential links to infections like progressive multifocal leukoencephalopathy (PML) and its role as a response biomarker, are not fully understood.

Purpose of the Study:

  • To investigate risk factors associated with dimethyl fumarate-induced lymphopenia in MS patients.
  • To assess the relationship between lymphopenia and treatment failure in a real-world MS cohort.
  • To evaluate the predictive value of lymphopenia for clinical response to DMF.

Main Methods:

  • Retrospective cohort study.
  • Involved 221 patients treated with DMF at an academic medical center from March 2013 to February 2015.
  • Analysis of risk factors for lymphopenia and correlation with clinical outcomes.

Main Results:

  • 17% of patients developed Grade 2-3 lymphopenia, which persisted throughout DMF treatment.
  • Risk factors for moderate to severe lymphopenia included older age (>55), lower baseline absolute lymphocyte count, and recent natalizumab exposure.
  • Lymphopenia did not predict a favorable clinical response or indicate breakthrough MS activity.

Conclusions:

  • A significant proportion of MS patients on DMF experience lymphopenia, often persistent if Grade 2 or higher.
  • Close monitoring of lymphocyte counts and awareness of infection risks are crucial for older patients and those transitioning from natalizumab.
  • Lymphopenia's role as a biomarker for DMF efficacy in MS requires further investigation.
Keywords:
Multiple sclerosisdimethyl fumaratedrug safetylymphopeniaprogressive multifocal leukoencephalopathy

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