To investigate risk factors for developing lymphopenia during dimethyl fumarate(DMF) treatment in patients with multiple sclerosis(MS) the following outcomes were collected: body mass index(BMI), baseline lymphocytes, age and gender.

DMF is associated with lymphopenia. Risk-management should be performed according to summary of product characteristics (SPC) when grade II or more severe lymphopenia is detected. Risk factors for developing lymphopenia in DMF-treated patients is currently only sparsely studied.

Retrospective cohort study of all Danish MS patients prescribed DMF at six clinics in two regions with a catchment area of 2.1 million citizens between May 2014 and September 2017(n=475). 7408 blood samples were included in the study.

Lymphopenia grade II/ III was detected in 30.8% of patients, of which 24.4 percentage point developed grade II and 6.4 percentage point grade III. No association between a low BMI and lymphopenia was found. Patients older than 55 years had an odds ratio(OR) of 3.58[95%-CI:1.79-7.62], p< 0.001 towards developing grade II-IV lymphopenia. Patients with low or low-normal baseline lymphocytes were at higher risk for developing lymphopenia. Patients with baseline lymphocyte counts(BLC) between 1.0-1.49·10⁹/l had an OR of 5.48 [CI:3.17-9.19], p≤0.0001 of developing lymphopenia. The combination of low BLC and age above 55yrs presented an OR of 10.21 [95%-CI:2.55-46.1], p<0.0005.

µþ³¢°ä&²µ³Ù;2,5·10⁹/l showed an OR of 0.11[95%-CI:0.01-0.66], p<0.01. 32.2% of patients discontinued DMF-treatment (25.9% and 48.8% in Region 1 and Region 2, respectively). OR for discontinuation in Region 1 compared to Region 2 was 2.72[95%-CI:1.77-4.18], p≤0.0001, and OR:4.25[95%-CI:2.66-6.81], p≤0.0001 if pregnancy and relapse discontinuations were excluded.

Patients with low BLCs and/or age above 55yrs present a markedly increased risk for developing lymphopenia. Vice versa low BLCs and low age seems protective. Lymphopenia is not related to BMI. Differences regarding discontinuation rates between clinics and regions were found, suggesting differences in management strategy despite national treatment guidelines.