Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis

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...

Descripción completa

Detalles Bibliográficos
Autores: Sainz de la Maza, Susana, Sabín Muñoz, Julia, Pilo de la Fuente, Belén, Thuissard Vasallo, Israel John, Andreu Vázquez, Cristina, Galán Sánchez-Seco, V., Salgado Cámara, Paula, Costa Frossard, Lucienne, Monreal, Enric, Aladro Benito, Yolanda, Et al.
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Europea (UEM)
Repositorio:ABACUS. Repositorio de Producción Científica
Idioma:inglés
OAI Identifier:oai:abacus.universidadeuropea.com:11268/11519
Acceso en línea:http://hdl.handle.net/11268/11519
Access Level:acceso abierto
Palabra clave:Esclerosis múltiple
Dimetilfumaratospanish
Linfopenia
Farmacología
Enfermedad del sistema nervioso
Cáncer
Descripción
Sumario: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: 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: 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: 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: 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.