@article{ce3e002b46cb41d78b4033f9b98b6d86,
title = "Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing–remitting multiple sclerosis",
abstract = "Background and purpose: 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. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A 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 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. Results: In all, 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 (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%–40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (−33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. Conclusion: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.",
keywords = "age, dimethyl fumarate, disease outcomes, lymphocyte count, multiple sclerosis, NEDA, treatment response",
author = "E. Tsantes and E. Curti and D. Ferraro and A. Lugaresi and E. Baldi and S. Montepietra and P. Immovilli and Simone, {A. M.} and L. Mancinelli and S. Strumia and F. Vitetta and M. Foschi and C. Ferri and C. Ferrarini and P. Sola and F. Granella",
note = "Funding Information: E.T. reports personal fees and non‐financial support from Merck & Co., personal fees from Almirall, personal fees and non‐financial support from Roche, non‐financial support from Biogen, non‐financial support from Sanofi, non‐financial support from Novartis, outside the submitted work. E.C. reports personal fees and non‐financial support from Merck & Co., personal fees and non‐financial support from Novartis, non‐financial support from Biogen, non‐financial support from Teva Pharmaceutical Industries, non‐financial support from Sanofi Genzyme, non‐financial support from Roche, outside the submitted work. D.F. has received travel grants and/or speaker honoraria from Merck, Biogen, Roche, Sanofi, Teva, outside the submitted work. A.L. reports personal fees from Biogen, Merck Serono, Roche Sanofi/Genzyme, Teva and Mylan, grants and personal fees from Novartis Pharma, outside the submitted work. E.B. reports grants from participating in a sponsored multicentre study, outside the submitted work. S.M. has nothing to disclose. P.I. reports honoraria for advisory boards from Merck and Roche, honoraria for frontal lessons from Biogen and publication fees from Novartis, outside the submitted work. A.M.S. has nothing to disclose. L.M. has nothing to disclose. S.S. has nothing to disclose. F.V. has received travel grants and/or speaker honoraria from Merck and Teva, outside the submitted work. M.F. reports involvement in clinical trials from Biogen and Roche and the receipt of travel grants from Sanofi‐Genzyme and from Roche, during the conduct of the study, outside the submitted work. C.F. has nothing to disclose. P.S. has received travel grants from Merck, Biogen, Roche, Sanofi, Teva, outside the submitted work. F.G. reports grants, personal fees and non‐financial support from Roche, grants, personal fees and non‐financial support from Biogen, personal fees and non‐financial support from Sanofi, personal fees and non‐financial support from Merck & Co., personal fees from Novartis, outside the submitted work. Publisher Copyright: {\textcopyright} 2020 European Academy of Neurology Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
doi = "10.1111/ene.14538",
language = "English",
volume = "28",
pages = "269--277",
journal = "European Journal of Neurology",
issn = "1351-5101",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "1",
}