Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis.
Dimethyl fumarate
Lymphopenia
Multiple sclerosis
Risk factors
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
03
12
2021
revised:
16
01
2022
accepted:
03
02
2022
pubmed:
13
2
2022
medline:
8
4
2022
entrez:
12
2
2022
Statut:
ppublish
Résumé
Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.
Sections du résumé
BACKGROUND
BACKGROUND
Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter.
OBJECTIVES
OBJECTIVE
To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia.
METHODS
METHODS
In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve.
RESULTS
RESULTS
Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia.
CONCLUSIONS
CONCLUSIONS
A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.
Identifiants
pubmed: 35150979
pii: S2211-0348(22)00184-5
doi: 10.1016/j.msard.2022.103669
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Dimethyl Fumarate
FO2303MNI2
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
103669Informations de copyright
Copyright © 2022. Published by Elsevier B.V.