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...

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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
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spelling Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosisSainz de la Maza, SusanaSabín Muñoz, JuliaPilo de la Fuente, BelénThuissard Vasallo, Israel JohnAndreu Vázquez, CristinaGalán Sánchez-Seco, V.Salgado Cámara, PaulaCosta Frossard, LucienneMonreal, EnricAladro Benito, YolandaEt al.Esclerosis múltipleDimetilfumaratospanishLinfopeniaFarmacologíaEnfermedad del sistema nerviosoCáncerBackground: 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.20222022-07-2220222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articlehttp://hdl.handle.net/11268/11519reponame:ABACUS. Repositorio de Producción Científicainstname:Universidad Europea (UEM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:abacus.universidadeuropea.com:11268/115192026-06-11T12:41:27Z
dc.title.none.fl_str_mv Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
title Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
spellingShingle Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
Sainz de la Maza, Susana
Esclerosis múltiple
Dimetilfumaratospanish
Linfopenia
Farmacología
Enfermedad del sistema nervioso
Cáncer
title_short Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
title_full Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
title_fullStr Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
title_full_unstemmed Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
title_sort Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis
dc.creator.none.fl_str_mv 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.
author Sainz de la Maza, Susana
author_facet 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.
author_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Esclerosis múltiple
Dimetilfumaratospanish
Linfopenia
Farmacología
Enfermedad del sistema nervioso
Cáncer
topic Esclerosis múltiple
Dimetilfumaratospanish
Linfopenia
Farmacología
Enfermedad del sistema nervioso
Cáncer
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-07-22
2022
2022-01-01
2022
2022-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/11268/11519
url http://hdl.handle.net/11268/11519
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:ABACUS. Repositorio de Producción Científica
instname:Universidad Europea (UEM)
instname_str Universidad Europea (UEM)
reponame_str ABACUS. Repositorio de Producción Científica
collection ABACUS. Repositorio de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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