Relapses in MS Patients Treated with DMF with No Variation in Lymphocyte Counts

Background: Dimethyl fumarate (DMF, Tecfidera®) has proven to be effective in relapsing multiple sclerosis by reducing clinical relapses and MRI activity.  In the pivotal clinical trials the proportion of patients with a relapse was 29%. A drop of 30% in the mean lymphocyte counts (LC) was identified, with the majority remaining above the lower limit of normal (0.9 x10⁹/L).  A drop in LC to <0.5x10⁹/L was identified in 6% of participants. This degree of lymphocytopenia has recently been identified as a potential contributor to the development of progressive multifocal leukoencephalopathy in patients taking DMF. It has not been established if a decrease in LC is a contributor to the beneficial effects of the drug. 

Objectives: To evaluate the clinical characteristics of a cohort of patients that did not have any change in their LC while on DMF to identify a possible therapeutic role of a decrease in LC.   

Methods:   One hundred and sixty three individuals (mean age 46.1 ±2.4, 76% females) began treatment with DMF at the Oklahoma Medical Research Foundation MS Center of Excellence between April 2013 and May 2015. DMF treatment duration ranged from 6 to 30 months (mean 19.2 ±2.4). Disease duration was 9.4±1.2 years.  Lymphocyte counts were evaluated prior to starting therapy and every six months after the first dose. 

Results: The mean baseline LC was 2.13x10⁹/L and the nadir 1.21x10⁹/L. The mean decrease of LC for the entire cohort was 0.92x10⁹/L ±.06, representing a 43% drop. A total of 15 patients (9.2%) did not experience any change in lymphocyte count throughout, defined as less than 10% from baseline.  In the cohort with unchanged LC, 4 individuals had a relapse during follow up, representing 26.6% of this subgroup.

Conclusions: Our cohort had a higher drop in LC than what was identified in clinical trials. The proportion of patients with a relapse in the group with no change in the LC was similar to the one reported in the pivotal trials, suggesting that a decrease in circulating lymphocytes is not a conditioning factor for efficacy in DMF.  Larger cohorts and longer follow up are necessary to determine if a reduction in LC is involved in the clinical benefits of DMF in MS.