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, de la Maza, SS, Alvarez-Cermeno, JC, Izquierdo, G, Paramo, D, Oliva, P, Casanova, B, Aguera-Morales, E, Franciotta, D, Gastaldi, M, Fernandez, 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, Gonzalez, I, Alvarez, E, Ramo, C, Caminero, AB, Aladro, Y, Calles, C, Eguia, P, Belenguer-Benavides, A, Ramio-Torrenta, L, Quintana, E, Martinez-Rodriguez, JE, Oterino, A, de Silanes, CL, Casanova, LI, Landete, L, Frederiksen, J, Bsteh, G, Mulero, P, Comabella, M, Hernandez, MA, Espino, M, Prieto, JM, Perez, D, Otano, M, Padilla, F, Garcia-Merino, JA, Navarro, L, Muriel, A, Frossard, LC, Villar, LM
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p6472
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones6472
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, Fde la Maza, SSAlvarez-Cermeno, JCIzquierdo, GParamo, DOliva, PCasanova, BAguera-Morales, EFranciotta, DGastaldi, MFernandez, OUrbaneja, PGarcia-Dominguez, JMRomero, FLaroni, AUccelli, APerez-Sempere, ASaiz, ABlanco, YGalimberti, DScarpini, EEspejo, CMontalban, XRasche, LPaul, FGonzalez, IAlvarez, ERamo, CCaminero, ABAladro, YCalles, CEguia, PBelenguer-Benavides, ARamio-Torrenta, LQuintana, EMartinez-Rodriguez, JEOterino, Ade Silanes, CLCasanova, LILandete, LFrederiksen, JBsteh, GMulero, PComabella, MHernandez, MAEspino, MPrieto, JMPerez, DOtano, MPadilla, FGarcia-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://isabial.portalinvestigacion.com/publicaciones6472Frontiers in NeurologyISSN: 16642295reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p64722026-06-12T10:20:37Z
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
de la Maza, SS
Alvarez-Cermeno, JC
Izquierdo, G
Paramo, D
Oliva, P
Casanova, B
Aguera-Morales, E
Franciotta, D
Gastaldi, M
Fernandez, 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
Gonzalez, I
Alvarez, E
Ramo, C
Caminero, AB
Aladro, Y
Calles, C
Eguia, P
Belenguer-Benavides, A
Ramio-Torrenta, L
Quintana, E
Martinez-Rodriguez, JE
Oterino, A
de Silanes, CL
Casanova, LI
Landete, L
Frederiksen, J
Bsteh, G
Mulero, P
Comabella, M
Hernandez, MA
Espino, M
Prieto, JM
Perez, D
Otano, M
Padilla, F
Garcia-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
de la Maza, SS
Alvarez-Cermeno, JC
Izquierdo, G
Paramo, D
Oliva, P
Casanova, B
Aguera-Morales, E
Franciotta, D
Gastaldi, M
Fernandez, 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
Gonzalez, I
Alvarez, E
Ramo, C
Caminero, AB
Aladro, Y
Calles, C
Eguia, P
Belenguer-Benavides, A
Ramio-Torrenta, L
Quintana, E
Martinez-Rodriguez, JE
Oterino, A
de Silanes, CL
Casanova, LI
Landete, L
Frederiksen, J
Bsteh, G
Mulero, P
Comabella, M
Hernandez, MA
Espino, M
Prieto, JM
Perez, D
Otano, M
Padilla, F
Garcia-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
de la Maza, SS
Alvarez-Cermeno, JC
Izquierdo, G
Paramo, D
Oliva, P
Casanova, B
Aguera-Morales, E
Franciotta, D
Gastaldi, M
Fernandez, 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
Gonzalez, I
Alvarez, E
Ramo, C
Caminero, AB
Aladro, Y
Calles, C
Eguia, P
Belenguer-Benavides, A
Ramio-Torrenta, L
Quintana, E
Martinez-Rodriguez, JE
Oterino, A
de Silanes, CL
Casanova, LI
Landete, L
Frederiksen, J
Bsteh, G
Mulero, P
Comabella, M
Hernandez, MA
Espino, M
Prieto, JM
Perez, D
Otano, M
Padilla, F
Garcia-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
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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://isabial.portalinvestigacion.com/publicaciones6472
url https://isabial.portalinvestigacion.com/publicaciones6472
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-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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