Incidence of persistent lymphopenia in people with multiple sclerosis on dimethyl fumarate

Abstract

BackgroundDimethyl fumarate (DMF) is a disease modifying therapy (DMT) used in the management of Multiple Sclerosis (MS). Lymphopenia occurs in approximately 30% of people receiving this medication. The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication in the context of persistent lymphopenia, because of an increased risk of progressive multifocal leukoencephalopathy (PML). It is therefore important for clinicians and patients to be aware of the frequency of persistent, moderate-severe lymphopenia in order to make informed decisions regarding drug choice and safety monitoring. MethodsWe reviewed medical records of 156 people with MS (PwMS) started on DMF between 2014 and 2020, who received at least 6 months of treatment, in order to identify the incidence and duration of persistent lymphopenia. ResultTen were excluded due to missing data. In 146 patients, treated for 30.7 months (mean), 16 (11%) were found to experience persistent moderate lymphopenia (0.5–0.7 × 109/L) and 5 (3%) experienced persistent severe lymphopenia (<0.5 × 109/L). Of the 5 patients with persistent severe lymphopenia, 3 discontinued DMF. Two cases stopped directly due to SPC recommendations and after 6-months no further DMTs were initiated. Treatment was withdrawn in a further case due to lack of efficacy. Two cases remained on DMF as their persistent severe lymphopenia predated SPC revision. Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respectively. Increased age was a predictor for persistent lymphopenia (B = 0.071, p = 0.004) while sex, and previous DMT were not.