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 I, Tejeda-Velarde A, Alvarez-Lafuente R, Arroyo R, Hegen H, Deisenhammer F, Sainz de la Maza S, Alvarez-Cermeño JC, Izquierdo G, Paramo D, Oliva P, Casanova B, Agüera-Morales E, Franciotta D, Gastaldi M, Fernández O, Urbaneja P, Garcia-Dominguez JM, Romero F, Laroni A, Uccelli A, Perez-Sempere A, Saiz A, Blanco Y, Galimberti D, Scarpini E, Espejo C, Montalban X, Rasche L, Paul F, González I, Álvarez E, Ramo C, Caminero AB, Aladro Y, Calles C, Eguía P, Belenguer-Benavides A, Ramió-Torrentà L, Quintana E, Martínez-Rodríguez JE, Oterino A, López de Silanes C, Casanova LI, Landete L, Frederiksen J, Bsteh G, Mulero P, Comabella M, Hernández MA, Espiño M, Prieto JM, Pérez D, Otano M, Padilla F, García-Merino JA, Navarro L, Muriel A, Frossard LC, Villar LM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p8697
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/8697
Access Level:acceso abierto
Palabra clave:multiple sclerosis
demyelinating diseases
biomarkers
natalizumab
progressive multifocal leucoencephalopathy
disease modifying treatments
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spelling New Algorithms Improving PML Risk Stratification in MS Patients Treated With NatalizumabToboso ITejeda-Velarde AAlvarez-Lafuente RArroyo RHegen HDeisenhammer FSainz de la Maza SAlvarez-Cermeño JCIzquierdo GParamo DOliva PCasanova BAgüera-Morales EFranciotta DGastaldi MFernández OUrbaneja PGarcia-Dominguez JMRomero FLaroni AUccelli APerez-Sempere ASaiz ABlanco YGalimberti DScarpini EEspejo CMontalban XRasche LPaul FGonzález IÁlvarez ERamo CCaminero ABAladro YCalles CEguía PBelenguer-Benavides ARamió-Torrentà LQuintana EMartínez-Rodríguez JEOterino ALópez de Silanes CCasanova LILandete LFrederiksen JBsteh GMulero PComabella MHernández MAEspiño MPrieto JMPérez DOtano MPadilla FGarcía-Merino JANavarro LMuriel AFrossard LCVillar LMmultiple sclerosisdemyelinating diseasesbiomarkersnatalizumabprogressive multifocal leucoencephalopathydisease modifying treatmentsOverview: 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 0.5, 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 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.FRONTIERS MEDIA SA2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/8697Frontiers in NeurologyISSN: 16642295reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p86972026-06-11T12:45:17Z
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 I
multiple sclerosis
demyelinating diseases
biomarkers
natalizumab
progressive multifocal leucoencephalopathy
disease modifying treatments
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 I
Tejeda-Velarde A
Alvarez-Lafuente R
Arroyo R
Hegen H
Deisenhammer F
Sainz de la Maza S
Alvarez-Cermeño JC
Izquierdo G
Paramo D
Oliva P
Casanova B
Agüera-Morales E
Franciotta D
Gastaldi M
Fernández O
Urbaneja P
Garcia-Dominguez JM
Romero F
Laroni A
Uccelli A
Perez-Sempere A
Saiz A
Blanco Y
Galimberti D
Scarpini E
Espejo C
Montalban X
Rasche L
Paul F
González I
Álvarez E
Ramo C
Caminero AB
Aladro Y
Calles C
Eguía P
Belenguer-Benavides A
Ramió-Torrentà L
Quintana E
Martínez-Rodríguez JE
Oterino A
López de Silanes C
Casanova LI
Landete L
Frederiksen J
Bsteh G
Mulero P
Comabella M
Hernández MA
Espiño M
Prieto JM
Pérez D
Otano M
Padilla F
García-Merino JA
Navarro L
Muriel A
Frossard LC
Villar LM
author Toboso I
author_facet Toboso I
Tejeda-Velarde A
Alvarez-Lafuente R
Arroyo R
Hegen H
Deisenhammer F
Sainz de la Maza S
Alvarez-Cermeño JC
Izquierdo G
Paramo D
Oliva P
Casanova B
Agüera-Morales E
Franciotta D
Gastaldi M
Fernández O
Urbaneja P
Garcia-Dominguez JM
Romero F
Laroni A
Uccelli A
Perez-Sempere A
Saiz A
Blanco Y
Galimberti D
Scarpini E
Espejo C
Montalban X
Rasche L
Paul F
González I
Álvarez E
Ramo C
Caminero AB
Aladro Y
Calles C
Eguía P
Belenguer-Benavides A
Ramió-Torrentà L
Quintana E
Martínez-Rodríguez JE
Oterino A
López de Silanes C
Casanova LI
Landete L
Frederiksen J
Bsteh G
Mulero P
Comabella M
Hernández MA
Espiño M
Prieto JM
Pérez D
Otano M
Padilla F
García-Merino JA
Navarro L
Muriel A
Frossard LC
Villar LM
author_role author
author2 Tejeda-Velarde A
Alvarez-Lafuente R
Arroyo R
Hegen H
Deisenhammer F
Sainz de la Maza S
Alvarez-Cermeño JC
Izquierdo G
Paramo D
Oliva P
Casanova B
Agüera-Morales E
Franciotta D
Gastaldi M
Fernández O
Urbaneja P
Garcia-Dominguez JM
Romero F
Laroni A
Uccelli A
Perez-Sempere A
Saiz A
Blanco Y
Galimberti D
Scarpini E
Espejo C
Montalban X
Rasche L
Paul F
González I
Álvarez E
Ramo C
Caminero AB
Aladro Y
Calles C
Eguía P
Belenguer-Benavides A
Ramió-Torrentà L
Quintana E
Martínez-Rodríguez JE
Oterino A
López de Silanes C
Casanova LI
Landete L
Frederiksen J
Bsteh G
Mulero P
Comabella M
Hernández MA
Espiño M
Prieto JM
Pérez D
Otano M
Padilla F
García-Merino JA
Navarro L
Muriel A
Frossard LC
Villar LM
author2_role author
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author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
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author
dc.subject.none.fl_str_mv multiple sclerosis
demyelinating diseases
biomarkers
natalizumab
progressive multifocal leucoencephalopathy
disease modifying treatments
topic multiple sclerosis
demyelinating diseases
biomarkers
natalizumab
progressive multifocal leucoencephalopathy
disease modifying treatments
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 0.5, 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 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
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 https://fisabio.portalinvestigacion.com/publicaciones/8697
url https://fisabio.portalinvestigacion.com/publicaciones/8697
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Neurology
ISSN: 16642295
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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