Lymphopaenia following dimethyl fumarate

Longbrake EE, Naismith RT, Parks BJ, Wu GF, Cross AH. Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance. Mult Scler J Exp Transl Clin. 2015;1. pii: 2055217315596994. 

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 centre 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 lymphopaenia while on DMF. Lymphopaenia was not predictive of good clinical response or of breakthrough MS activity on DMF.
CONCLUSIONS: Lymphopaenia 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.

PML has occurred in people treated with DMF and this has been associated with low numbers of white blood cells in the CNS. This occurred with low frequency in people with MS. However if it did occur then the it did not resolve. ProfG has predicted more cases of PML will occur on DMF at counts above 500. He thinks previous natalizumab therapy and older age will also emerge as a risk factor in the new cases.

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