Background Dimethyl fumarate (DMF) is a disease modifying therapy (DMT) used to manage Multiple Sclerosis (MS). The recently revised Summary of Product Characteristics (SPC) recommends increased monitoring or cessation of this medication for persistent (> 6 months) lymphopenia, because of an increased risk of Progressive Multifocal Leukoencephalopathy. Awareness of the frequency of persistent lymphopenia will guide clinical decisions regarding drug choice and safety monitoring.

Methods Medical records of 146 patients with MS, started on DMF between 2014-2020 who received > 6 months of treatment were reviewed to identify the incidence, duration, and risk factors of persistent lymphopenia.

Results Overall, 16 (11%) people with MS taking DMF experienced persistent moderate lymphopenia (0.5-0.7x109/L for > 6m) and 5 (3%) experienced persistent severe lymphopenia (<0.5 x 109/L for > 6m). Mean times to persistent moderate and severe lymphopenia were 10.6 months and 25.5 months respec- tively. Increased age was a predictor for persistent lymphopenia (B=0.071, p=0.004); sex and previous DMT were not.

Conclusion Persistent moderate – severe lymphopenia is relatively common in people on DMF. More robust guidelines for both risk/benefit of continuing DMF despite persistent lymphopenia, and DMT sequencing following DMF in people with lymphopenia are required.