New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

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New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab. / Toboso, Inmaculada; Tejeda-Velarde, Amalia; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Hegen, Harald; Deisenhammer, Florian; Sainz de la Maza, Susana; Alvarez-Cermeño, José C.; Izquierdo, Guillermo; Paramo, Dolores; Oliva, Pedro; Casanova, Bonaventura; Agüera-Morales, Eduardo; Franciotta, Diego; Gastaldi, Matteo; Fernández, Oscar; Urbaneja, Patricia; Garcia-Dominguez, José M.; Romero, Fernando; Laroni, Alicia; Uccelli, Antonio; Perez-Sempere, Angel; Saiz, Albert; Blanco, Yolanda; Galimberti, Daniela; Scarpini, Elio; Espejo, Carmen; Montalban, Xavier; Rasche, Ludwig; Paul, Friedemann; González, Inés; Álvarez, Elena; Ramo, Cristina; Caminero, Ana B.; Aladro, Yolanda; Calles, Carmen; Eguía, Pablo; Belenguer-Benavides, Antonio; Ramió-Torrentà, Lluis; Quintana, Ester; Martínez-Rodríguez, José E.; Oterino, Agustín; López de Silanes, Carlos; Casanova, Luis I.; Landete, Lamberto; Frederiksen, Jette; Bsteh, Gabriel; Mulero, Patricia; Comabella, Manuel; Hernández, Miguel A.; Espiño, Mercedes; Prieto, José M.; Pérez, Domingo; Otano, María; Padilla, Francisco; García-Merino, Juan A.; Navarro, Laura; Muriel, Alfonso; Frossard, Lucienne Costa; Villar, Luisa M.

I: Frontiers in Neurology, Bind 11, 579438, 17.12.2020.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

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 2020, 'New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab', Frontiers in Neurology, bind 11, 579438. https://doi.org/10.3389/fneur.2020.579438

APA

Toboso, I., Tejeda-Velarde, A., Alvarez-Lafuente, R., Arroyo, R., Hegen, H., Deisenhammer, F., Sainz de la Maza, S., Alvarez-Cermeño, J. C., Izquierdo, G., Paramo, D., Oliva, P., Casanova, B., Agüera-Morales, E., Franciotta, D., Gastaldi, M., Fernández, O., Urbaneja, P., Garcia-Dominguez, J. M., Romero, F., ... Villar, L. M. (2020). New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab. Frontiers in Neurology, 11, [579438]. https://doi.org/10.3389/fneur.2020.579438

Vancouver

Toboso I, Tejeda-Velarde A, Alvarez-Lafuente R, Arroyo R, Hegen H, Deisenhammer F o.a. New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab. Frontiers in Neurology. 2020 dec. 17;11. 579438. https://doi.org/10.3389/fneur.2020.579438

Author

Toboso, Inmaculada ; Tejeda-Velarde, Amalia ; Alvarez-Lafuente, Roberto ; Arroyo, Rafael ; Hegen, Harald ; Deisenhammer, Florian ; Sainz de la Maza, Susana ; Alvarez-Cermeño, José C. ; Izquierdo, Guillermo ; Paramo, Dolores ; Oliva, Pedro ; Casanova, Bonaventura ; Agüera-Morales, Eduardo ; Franciotta, Diego ; Gastaldi, Matteo ; Fernández, Oscar ; Urbaneja, Patricia ; Garcia-Dominguez, José M. ; Romero, Fernando ; Laroni, Alicia ; Uccelli, Antonio ; Perez-Sempere, Angel ; Saiz, Albert ; Blanco, Yolanda ; Galimberti, Daniela ; Scarpini, Elio ; Espejo, Carmen ; Montalban, Xavier ; Rasche, Ludwig ; Paul, Friedemann ; González, Inés ; Álvarez, Elena ; Ramo, Cristina ; Caminero, Ana B. ; Aladro, Yolanda ; Calles, Carmen ; Eguía, Pablo ; Belenguer-Benavides, Antonio ; Ramió-Torrentà, Lluis ; Quintana, Ester ; Martínez-Rodríguez, José E. ; Oterino, Agustín ; López de Silanes, Carlos ; Casanova, Luis I. ; Landete, Lamberto ; Frederiksen, Jette ; Bsteh, Gabriel ; Mulero, Patricia ; Comabella, Manuel ; Hernández, Miguel A. ; Espiño, Mercedes ; Prieto, José M. ; Pérez, Domingo ; Otano, María ; Padilla, Francisco ; García-Merino, Juan A. ; Navarro, Laura ; Muriel, Alfonso ; Frossard, Lucienne Costa ; Villar, Luisa M. / New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab. I: Frontiers in Neurology. 2020 ; Bind 11.

Bibtex

@article{c20680cace5341cb9cc4fcab81736233,

title = "New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab",

abstract = "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.",

keywords = "biomarkers, demyelinating diseases, disease modifying treatments, multiple sclerosis, natalizumab, progressive multifocal leucoencephalopathy",

author = "Inmaculada Toboso and Amalia Tejeda-Velarde and Roberto Alvarez-Lafuente and Rafael Arroyo and Harald Hegen and Florian Deisenhammer and {Sainz de la Maza}, Susana and Alvarez-Cerme{\~n}o, {Jos{\'e} C.} and Guillermo Izquierdo and Dolores Paramo and Pedro Oliva and Bonaventura Casanova and Eduardo Ag{\"u}era-Morales and Diego Franciotta and Matteo Gastaldi and Oscar Fern{\'a}ndez and Patricia Urbaneja and Garcia-Dominguez, {Jos{\'e} M.} and Fernando Romero and Alicia Laroni and Antonio Uccelli and Angel Perez-Sempere and Albert Saiz and Yolanda Blanco and Daniela Galimberti and Elio Scarpini and Carmen Espejo and Xavier Montalban and Ludwig Rasche and Friedemann Paul and In{\'e}s Gonz{\'a}lez and Elena {\'A}lvarez and Cristina Ramo and Caminero, {Ana B.} and Yolanda Aladro and Carmen Calles and Pablo Egu{\'i}a and Antonio Belenguer-Benavides and Lluis Rami{\'o}-Torrent{\`a} and Ester Quintana and Mart{\'i}nez-Rodr{\'i}guez, {Jos{\'e} E.} and Agust{\'i}n Oterino and {L{\'o}pez de Silanes}, Carlos and Casanova, {Luis I.} and Lamberto Landete and Jette Frederiksen and Gabriel Bsteh and Patricia Mulero and Manuel Comabella and Hern{\'a}ndez, {Miguel A.} and Mercedes Espi{\~n}o and Prieto, {Jos{\'e} M.} and Domingo P{\'e}rez and Mar{\'i}a Otano and Francisco Padilla and Garc{\'i}a-Merino, {Juan A.} and Laura Navarro and Alfonso Muriel and Frossard, {Lucienne Costa} and Villar, {Luisa M.}",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Toboso, Tejeda-Velarde, Alvarez-Lafuente, Arroyo, Hegen, Deisenhammer, Sainz de la Maza, Alvarez-Cerme{\~n}o, Izquierdo, Paramo, Oliva, Casanova, Ag{\"u}era-Morales, Franciotta, Gastaldi, Fern{\'a}ndez, Urbaneja, Garcia-Dominguez, Romero, Laroni, Uccelli, Perez-Sempere, Saiz, Blanco, Galimberti, Scarpini, Espejo, Montalban, Rasche, Paul, Gonz{\'a}lez, {\'A}lvarez, Ramo, Caminero, Aladro, Calles, Egu{\'i}a, Belenguer-Benavides, Rami{\'o}-Torrent{\`a}, Quintana, Mart{\'i}nez-Rodr{\'i}guez, Oterino, L{\'o}pez de Silanes, Casanova, Landete, Frederiksen, Bsteh, Mulero, Comabella, Hern{\'a}ndez, Espi{\~n}o, Prieto, P{\'e}rez, Otano, Padilla, Garc{\'i}a-Merino, Navarro, Muriel, Frossard and Villar.",

year = "2020",

month = dec,

day = "17",

doi = "10.3389/fneur.2020.579438",

language = "English",

volume = "11",

journal = "Frontiers in Neurology",

issn = "1664-2295",

publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

AU - Toboso, Inmaculada

AU - Tejeda-Velarde, Amalia

AU - Alvarez-Lafuente, Roberto

AU - Arroyo, Rafael

AU - Hegen, Harald

AU - Deisenhammer, Florian

AU - Sainz de la Maza, Susana

AU - Alvarez-Cermeño, José C.

AU - Izquierdo, Guillermo

AU - Paramo, Dolores

AU - Oliva, Pedro

AU - Casanova, Bonaventura

AU - Agüera-Morales, Eduardo

AU - Franciotta, Diego

AU - Gastaldi, Matteo

AU - Fernández, Oscar

AU - Urbaneja, Patricia

AU - Garcia-Dominguez, José M.

AU - Romero, Fernando

AU - Laroni, Alicia

AU - Uccelli, Antonio

AU - Perez-Sempere, Angel

AU - Saiz, Albert

AU - Blanco, Yolanda

AU - Galimberti, Daniela

AU - Scarpini, Elio

AU - Espejo, Carmen

AU - Montalban, Xavier

AU - Rasche, Ludwig

AU - Paul, Friedemann

AU - González, Inés

AU - Álvarez, Elena

AU - Ramo, Cristina

AU - Caminero, Ana B.

AU - Aladro, Yolanda

AU - Calles, Carmen

AU - Eguía, Pablo

AU - Belenguer-Benavides, Antonio

AU - Ramió-Torrentà, Lluis

AU - Quintana, Ester

AU - Martínez-Rodríguez, José E.

AU - Oterino, Agustín

AU - López de Silanes, Carlos

AU - Casanova, Luis I.

AU - Landete, Lamberto

AU - Frederiksen, Jette

AU - Bsteh, Gabriel

AU - Mulero, Patricia

AU - Comabella, Manuel

AU - Hernández, Miguel A.

AU - Espiño, Mercedes

AU - Prieto, José M.

AU - Pérez, Domingo

AU - Otano, María

AU - Padilla, Francisco

AU - García-Merino, Juan A.

AU - Navarro, Laura

AU - Muriel, Alfonso

AU - Frossard, Lucienne Costa

AU - Villar, Luisa M.

N1 - Publisher Copyright: © Copyright © 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.

PY - 2020/12/17

Y1 - 2020/12/17

N2 - 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.

AB - 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.

KW - biomarkers

KW - demyelinating diseases

KW - disease modifying treatments

KW - multiple sclerosis

KW - natalizumab

KW - progressive multifocal leucoencephalopathy

U2 - 10.3389/fneur.2020.579438

DO - 10.3389/fneur.2020.579438

M3 - Journal article

C2 - 33408681

AN - SCOPUS:85098937296

VL - 11

JO - Frontiers in Neurology

JF - Frontiers in Neurology

SN - 1664-2295

M1 - 579438

ER -

ID: 269911569