Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis

BACKGROUND AND OBJECTIVE Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. OBJECTIVE To investigate if absolute lymphocyte count (ALC) decrease from baseline during DMF treatment is associated with clinical and MRI disease activity. Secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF treated patients. Methods- Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of six month-ALC drop on time to NEDA-3 status loss. NEDA-3 ("no evidence of disease activity") is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (HR 0.87, p = 0.01). A worse outcome in patients with lower ALC drop ( 40.5%), was observed (p=0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopenia cases occurred after 12 months of treatment. CONCLUSION A higher lymphocyte count drop at six months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.