Relationship between lymphopenia and disease activity in persons with multiple sclerosis treated with dimethyl fumarate

Background: Dimethyl fumarate (DMF) is a disease-modifying therapy (DMT) used to treat relapsing multiple sclerosis (MS). Its precise mechanism in treating MS involves nuclear factor erythroid-derived 2-related factor -dependent and-independent pathways. Lymphopenia, defined according to NIH Common Terminology for Adverse Events v5.0, is one potential adverse effect. It is unclear whether lymphopenia correlates with disease activity; existing studies have yielded conflicting results.& nbsp;Objective: To determine whether lymphopenia in DMF-treated persons with MS (PwMS) correlates with disease activity.& nbsp;Methods: A retrospective chart review of 66 PwMS treated with DMF between January 1, 2013 and September 30, 2020.& nbsp;Results: Participants who experienced lymphopenia were older (p < 0.001), and had a longer disease duration (p = 0.012) and lower baseline absolute lymphocyte count (ALC) (p < 0.001). Breakthrough disease activity was the most common reason for DMF discontinuation (53.0%). Lymphopenia occurred in 36.4%, with ALCs decreasing over the first 12 months of therapy before plateauing. Lymphopenia was associated with a trend towards reduced relapses (p = 0.059) and significantly improved MRI activity (p = 0.001) and no evidence of disease activity (NEDA-3) (p = 0.022), but not disability progression (p = 0.549). Persons with lymphopenia were significantly less likely to be treated with another DMT after DMF (p = 0.036).& nbsp;Conclusion: Risk factors for and rates of lymphopenia resembled existing data. Lymphopenia was associated with significantly improved MRI activity and achievement of NEDA-3, and whether PwMS were treated with another DMT after DMF. Further studies are required to clarify the mechanism of DMF, lymphocyte subsets and their relationship with disease activity, and which characteristics predict response to DMF.