Affiliation:
1. Department of Neurology, Washington University in St. Louis, USA
Abstract
Background Dimethyl fumarate (DMF), a disease-modifying therapy for multiple sclerosis (MS), causes lymphopenia in a fraction of patients. The clinical significance of this is unknown. Several cases of progressive multifocal leukoencephalopathy in lymphopenic fumarate-treated patients have raised concerns about drug safety. Since lymphocytes contribute to MS pathology, lymphopenia may also be a biomarker for response to the drug. Objective The objective of this manuscript is to evaluate risk factors for DMF-induced lymphopenia and drug failure in a real-world population of MS patients. Methods We conducted a retrospective cohort study of 221 patients prescribed DMF at a single academic medical center between March 2013 and February 2015. Results Grade 2–3 lymphopenia developed in 17% of the total cohort and did not resolve during DMF treatment. Older age (>55), lower baseline absolute lymphocyte count and recent natalizumab exposure increased the risk of developing moderate to severe lymphopenia while on DMF. Lymphopenia was not predictive of good clinical response or of breakthrough MS activity on DMF. Conclusions Lymphopenia develops in a significant minority of DMF-treated patients, and if grade 2 or worse, is unlikely to resolve while on the drug. Increased vigilance in lymphocyte monitoring and infection awareness is particularly warranted in older patients and those switching from natalizumab.
Subject
Cellular and Molecular Neuroscience,Clinical Neurology
Cited by
69 articles.
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