New algorithms improving PML risk stratification in MS patients treated with natalizumab

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis...

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Autores: Toboso, Inmaculada, Martínez Rodríguez, José Enrique, Villar, Luisa Maria
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/53408
Acceso en línea:http://hdl.handle.net/10230/53408
http://dx.doi.org/10.3389/fneur.2020.579438
Access Level:acceso abierto
Palabra clave:Biomarkers
Demyelinating diseases
Disease modifying treatments
Multiple sclerosis
Natalizumab
Progressive multifocal leucoencephalopathy
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spelling New algorithms improving PML risk stratification in MS patients treated with natalizumabToboso, InmaculadaMartínez Rodríguez, José EnriqueVillar, Luisa MariaBiomarkersDemyelinating diseasesDisease modifying treatmentsMultiple sclerosisNatalizumabProgressive multifocal leucoencephalopathyOverview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.Frontiers202220222020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/53408http://dx.doi.org/10.3389/fneur.2020.579438reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésCopyright © 2020 Toboso, Tejeda-Velarde, Alvarez-Lafuente, Arroyo, Hegen, Deisenhammer, Sainz de la Maza, Alvarez-Cermeño, Izquierdo, Paramo, Oliva, Casanova, Agüera-Morales, Franciotta, Gastaldi, Fernández, Urbaneja, Garcia-Dominguez, Romero, Laroni, Uccelli, Perez-Sempere, Saiz, Blanco, Galimberti, Scarpini, Espejo, Montalban, Rasche, Paul, González, Álvarez, Ramo, Caminero, Aladro, Calles, Eguía, Belenguer-Benavides, Ramió-Torrentà, Quintana, Martínez-Rodríguez, Oterino, López de Silanes, Casanova, Landete, Frederiksen, Bsteh, Mulero, Comabella, Hernández, Espiño, Prieto, Pérez, Otano, Padilla, García-Merino, Navarro, Muriel, Frossard and Villar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this jhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/534082026-05-29T05:05:01Z
dc.title.none.fl_str_mv New algorithms improving PML risk stratification in MS patients treated with natalizumab
title New algorithms improving PML risk stratification in MS patients treated with natalizumab
spellingShingle New algorithms improving PML risk stratification in MS patients treated with natalizumab
Toboso, Inmaculada
Biomarkers
Demyelinating diseases
Disease modifying treatments
Multiple sclerosis
Natalizumab
Progressive multifocal leucoencephalopathy
title_short New algorithms improving PML risk stratification in MS patients treated with natalizumab
title_full New algorithms improving PML risk stratification in MS patients treated with natalizumab
title_fullStr New algorithms improving PML risk stratification in MS patients treated with natalizumab
title_full_unstemmed New algorithms improving PML risk stratification in MS patients treated with natalizumab
title_sort New algorithms improving PML risk stratification in MS patients treated with natalizumab
dc.creator.none.fl_str_mv Toboso, Inmaculada
Martínez Rodríguez, José Enrique
Villar, Luisa Maria
author Toboso, Inmaculada
author_facet Toboso, Inmaculada
Martínez Rodríguez, José Enrique
Villar, Luisa Maria
author_role author
author2 Martínez Rodríguez, José Enrique
Villar, Luisa Maria
author2_role author
author
dc.subject.none.fl_str_mv Biomarkers
Demyelinating diseases
Disease modifying treatments
Multiple sclerosis
Natalizumab
Progressive multifocal leucoencephalopathy
topic Biomarkers
Demyelinating diseases
Disease modifying treatments
Multiple sclerosis
Natalizumab
Progressive multifocal leucoencephalopathy
description Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.
publishDate 2020
dc.date.none.fl_str_mv 2020
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/53408
http://dx.doi.org/10.3389/fneur.2020.579438
url http://hdl.handle.net/10230/53408
http://dx.doi.org/10.3389/fneur.2020.579438
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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