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

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 (...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in neurology 2020-12, Vol.11, p.579438-579438
Main Authors: 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
Format: Article
Language:English
Subjects:
biomarkers
demyelinating diseases
disease modifying treatments
multiple sclerosis
natalizumab
Neurology
progressive multifocal leucoencephalopathy
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43
cites cdi_FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43
container_end_page 579438
container_issue
container_start_page 579438
container_title Frontiers in neurology
container_volume 11
creator 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
description 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. 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
doi_str_mv 10.3389/fneur.2020.579438
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_c82f6fa684d240fe86a6b469a1788aa1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_c82f6fa684d240fe86a6b469a1788aa1</doaj_id><sourcerecordid>2476127527</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43</originalsourceid><addsrcrecordid>eNpVkctuFDEQRS0EIlHIB7BBXrKZwa-23RukKOIx0iREJAh2VrUfE4fu9mB3B8HX48mEKPHCLtt1T1XpIvSakiXnun0XRj_nJSOMLBvVCq6foUMqpVgw1jbPH8UH6LiUG1IXb1su-Ut0wLkgWmp6iH6c-9_4pN-kHKfroeDVsM3pNo4bfHG2xl9j-YkvpwxTDNHWPY04jvjsEl_Uix-ngq-yh8k7_L3q8TlM0Me_8wDdK_QiQF_88f15hL59_HB1-nmx_vJpdXqyXlghm2khqNShc7prFIBjInBmQSnaaUE72znXWu6EaDwTOhAmwQGX1nFNhaYEBD9Cqz3XJbgx2xwHyH9MgmjuHlLeGMhTtL03VrMgA0gtaiESvJYgOyFboEprAFpZ7_es7dwN3tk6YIb-CfTpzxivzSbdGqU00c0O8PYekNOv2ZfJDLFY3_cw-jQXw4SSlKmGqZpK96k2p1KyDw9lKDE7g82dwWZnsNkbXDVvHvf3oPhvJ_8HX7OjXQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2476127527</pqid></control><display><type>article</type><title>New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab</title><source>PubMed Central Free</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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. 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 &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;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 &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. 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.</description><identifier>ISSN: 1664-2295</identifier><identifier>EISSN: 1664-2295</identifier><identifier>DOI: 10.3389/fneur.2020.579438</identifier><identifier>PMID: 33408681</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>biomarkers ; demyelinating diseases ; disease modifying treatments ; multiple sclerosis ; natalizumab ; Neurology ; progressive multifocal leucoencephalopathy</subject><ispartof>Frontiers in neurology, 2020-12, Vol.11, p.579438-579438</ispartof><rights>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.</rights><rights>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. 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</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43</citedby><cites>FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780851/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780851/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33408681$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Toboso, Inmaculada</creatorcontrib><creatorcontrib>Tejeda-Velarde, Amalia</creatorcontrib><creatorcontrib>Alvarez-Lafuente, Roberto</creatorcontrib><creatorcontrib>Arroyo, Rafael</creatorcontrib><creatorcontrib>Hegen, Harald</creatorcontrib><creatorcontrib>Deisenhammer, Florian</creatorcontrib><creatorcontrib>Sainz de la Maza, Susana</creatorcontrib><creatorcontrib>Alvarez-Cermeño, José C</creatorcontrib><creatorcontrib>Izquierdo, Guillermo</creatorcontrib><creatorcontrib>Paramo, Dolores</creatorcontrib><creatorcontrib>Oliva, Pedro</creatorcontrib><creatorcontrib>Casanova, Bonaventura</creatorcontrib><creatorcontrib>Agüera-Morales, Eduardo</creatorcontrib><creatorcontrib>Franciotta, Diego</creatorcontrib><creatorcontrib>Gastaldi, Matteo</creatorcontrib><creatorcontrib>Fernández, Oscar</creatorcontrib><creatorcontrib>Urbaneja, Patricia</creatorcontrib><creatorcontrib>Garcia-Dominguez, José M</creatorcontrib><creatorcontrib>Romero, Fernando</creatorcontrib><creatorcontrib>Laroni, Alicia</creatorcontrib><creatorcontrib>Uccelli, Antonio</creatorcontrib><creatorcontrib>Perez-Sempere, Angel</creatorcontrib><creatorcontrib>Saiz, Albert</creatorcontrib><creatorcontrib>Blanco, Yolanda</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Scarpini, Elio</creatorcontrib><creatorcontrib>Espejo, Carmen</creatorcontrib><creatorcontrib>Montalban, Xavier</creatorcontrib><creatorcontrib>Rasche, Ludwig</creatorcontrib><creatorcontrib>Paul, Friedemann</creatorcontrib><creatorcontrib>González, Inés</creatorcontrib><creatorcontrib>Álvarez, Elena</creatorcontrib><creatorcontrib>Ramo, Cristina</creatorcontrib><creatorcontrib>Caminero, Ana B</creatorcontrib><creatorcontrib>Aladro, Yolanda</creatorcontrib><creatorcontrib>Calles, Carmen</creatorcontrib><creatorcontrib>Eguía, Pablo</creatorcontrib><creatorcontrib>Belenguer-Benavides, Antonio</creatorcontrib><creatorcontrib>Ramió-Torrentà, Lluis</creatorcontrib><creatorcontrib>Quintana, Ester</creatorcontrib><creatorcontrib>Martínez-Rodríguez, José E</creatorcontrib><creatorcontrib>Oterino, Agustín</creatorcontrib><creatorcontrib>López de Silanes, Carlos</creatorcontrib><creatorcontrib>Casanova, Luis I</creatorcontrib><creatorcontrib>Landete, Lamberto</creatorcontrib><creatorcontrib>Frederiksen, Jette</creatorcontrib><creatorcontrib>Bsteh, Gabriel</creatorcontrib><creatorcontrib>Mulero, Patricia</creatorcontrib><creatorcontrib>Comabella, Manuel</creatorcontrib><creatorcontrib>Hernández, Miguel A</creatorcontrib><creatorcontrib>Espiño, Mercedes</creatorcontrib><creatorcontrib>Prieto, José M</creatorcontrib><creatorcontrib>Pérez, Domingo</creatorcontrib><creatorcontrib>Otano, María</creatorcontrib><creatorcontrib>Padilla, Francisco</creatorcontrib><creatorcontrib>García-Merino, Juan A</creatorcontrib><creatorcontrib>Navarro, Laura</creatorcontrib><creatorcontrib>Muriel, Alfonso</creatorcontrib><creatorcontrib>Frossard, Lucienne Costa</creatorcontrib><creatorcontrib>Villar, Luisa M</creatorcontrib><title>New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab</title><title>Frontiers in neurology</title><addtitle>Front Neurol</addtitle><description>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. 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 &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;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 &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. 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.</description><subject>biomarkers</subject><subject>demyelinating diseases</subject><subject>disease modifying treatments</subject><subject>multiple sclerosis</subject><subject>natalizumab</subject><subject>Neurology</subject><subject>progressive multifocal leucoencephalopathy</subject><issn>1664-2295</issn><issn>1664-2295</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkctuFDEQRS0EIlHIB7BBXrKZwa-23RukKOIx0iREJAh2VrUfE4fu9mB3B8HX48mEKPHCLtt1T1XpIvSakiXnun0XRj_nJSOMLBvVCq6foUMqpVgw1jbPH8UH6LiUG1IXb1su-Ut0wLkgWmp6iH6c-9_4pN-kHKfroeDVsM3pNo4bfHG2xl9j-YkvpwxTDNHWPY04jvjsEl_Uix-ngq-yh8k7_L3q8TlM0Me_8wDdK_QiQF_88f15hL59_HB1-nmx_vJpdXqyXlghm2khqNShc7prFIBjInBmQSnaaUE72znXWu6EaDwTOhAmwQGX1nFNhaYEBD9Cqz3XJbgx2xwHyH9MgmjuHlLeGMhTtL03VrMgA0gtaiESvJYgOyFboEprAFpZ7_es7dwN3tk6YIb-CfTpzxivzSbdGqU00c0O8PYekNOv2ZfJDLFY3_cw-jQXw4SSlKmGqZpK96k2p1KyDw9lKDE7g82dwWZnsNkbXDVvHvf3oPhvJ_8HX7OjXQ</recordid><startdate>20201217</startdate><enddate>20201217</enddate><creator>Toboso, Inmaculada</creator><creator>Tejeda-Velarde, Amalia</creator><creator>Alvarez-Lafuente, Roberto</creator><creator>Arroyo, Rafael</creator><creator>Hegen, Harald</creator><creator>Deisenhammer, Florian</creator><creator>Sainz de la Maza, Susana</creator><creator>Alvarez-Cermeño, José C</creator><creator>Izquierdo, Guillermo</creator><creator>Paramo, Dolores</creator><creator>Oliva, Pedro</creator><creator>Casanova, Bonaventura</creator><creator>Agüera-Morales, Eduardo</creator><creator>Franciotta, Diego</creator><creator>Gastaldi, Matteo</creator><creator>Fernández, Oscar</creator><creator>Urbaneja, Patricia</creator><creator>Garcia-Dominguez, José M</creator><creator>Romero, Fernando</creator><creator>Laroni, Alicia</creator><creator>Uccelli, Antonio</creator><creator>Perez-Sempere, Angel</creator><creator>Saiz, Albert</creator><creator>Blanco, Yolanda</creator><creator>Galimberti, Daniela</creator><creator>Scarpini, Elio</creator><creator>Espejo, Carmen</creator><creator>Montalban, Xavier</creator><creator>Rasche, Ludwig</creator><creator>Paul, Friedemann</creator><creator>González, Inés</creator><creator>Álvarez, Elena</creator><creator>Ramo, Cristina</creator><creator>Caminero, Ana B</creator><creator>Aladro, Yolanda</creator><creator>Calles, Carmen</creator><creator>Eguía, Pablo</creator><creator>Belenguer-Benavides, Antonio</creator><creator>Ramió-Torrentà, Lluis</creator><creator>Quintana, Ester</creator><creator>Martínez-Rodríguez, José E</creator><creator>Oterino, Agustín</creator><creator>López de Silanes, Carlos</creator><creator>Casanova, Luis I</creator><creator>Landete, Lamberto</creator><creator>Frederiksen, Jette</creator><creator>Bsteh, Gabriel</creator><creator>Mulero, Patricia</creator><creator>Comabella, Manuel</creator><creator>Hernández, Miguel A</creator><creator>Espiño, Mercedes</creator><creator>Prieto, José M</creator><creator>Pérez, Domingo</creator><creator>Otano, María</creator><creator>Padilla, Francisco</creator><creator>García-Merino, Juan A</creator><creator>Navarro, Laura</creator><creator>Muriel, Alfonso</creator><creator>Frossard, Lucienne Costa</creator><creator>Villar, Luisa M</creator><general>Frontiers Media S.A</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20201217</creationdate><title>New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab</title><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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>biomarkers</topic><topic>demyelinating diseases</topic><topic>disease modifying treatments</topic><topic>multiple sclerosis</topic><topic>natalizumab</topic><topic>Neurology</topic><topic>progressive multifocal leucoencephalopathy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Toboso, Inmaculada</creatorcontrib><creatorcontrib>Tejeda-Velarde, Amalia</creatorcontrib><creatorcontrib>Alvarez-Lafuente, Roberto</creatorcontrib><creatorcontrib>Arroyo, Rafael</creatorcontrib><creatorcontrib>Hegen, Harald</creatorcontrib><creatorcontrib>Deisenhammer, Florian</creatorcontrib><creatorcontrib>Sainz de la Maza, Susana</creatorcontrib><creatorcontrib>Alvarez-Cermeño, José C</creatorcontrib><creatorcontrib>Izquierdo, Guillermo</creatorcontrib><creatorcontrib>Paramo, Dolores</creatorcontrib><creatorcontrib>Oliva, Pedro</creatorcontrib><creatorcontrib>Casanova, Bonaventura</creatorcontrib><creatorcontrib>Agüera-Morales, Eduardo</creatorcontrib><creatorcontrib>Franciotta, Diego</creatorcontrib><creatorcontrib>Gastaldi, Matteo</creatorcontrib><creatorcontrib>Fernández, Oscar</creatorcontrib><creatorcontrib>Urbaneja, Patricia</creatorcontrib><creatorcontrib>Garcia-Dominguez, José M</creatorcontrib><creatorcontrib>Romero, Fernando</creatorcontrib><creatorcontrib>Laroni, Alicia</creatorcontrib><creatorcontrib>Uccelli, Antonio</creatorcontrib><creatorcontrib>Perez-Sempere, Angel</creatorcontrib><creatorcontrib>Saiz, Albert</creatorcontrib><creatorcontrib>Blanco, Yolanda</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Scarpini, Elio</creatorcontrib><creatorcontrib>Espejo, Carmen</creatorcontrib><creatorcontrib>Montalban, Xavier</creatorcontrib><creatorcontrib>Rasche, Ludwig</creatorcontrib><creatorcontrib>Paul, Friedemann</creatorcontrib><creatorcontrib>González, Inés</creatorcontrib><creatorcontrib>Álvarez, Elena</creatorcontrib><creatorcontrib>Ramo, Cristina</creatorcontrib><creatorcontrib>Caminero, Ana B</creatorcontrib><creatorcontrib>Aladro, Yolanda</creatorcontrib><creatorcontrib>Calles, Carmen</creatorcontrib><creatorcontrib>Eguía, Pablo</creatorcontrib><creatorcontrib>Belenguer-Benavides, Antonio</creatorcontrib><creatorcontrib>Ramió-Torrentà, Lluis</creatorcontrib><creatorcontrib>Quintana, Ester</creatorcontrib><creatorcontrib>Martínez-Rodríguez, José E</creatorcontrib><creatorcontrib>Oterino, Agustín</creatorcontrib><creatorcontrib>López de Silanes, Carlos</creatorcontrib><creatorcontrib>Casanova, Luis I</creatorcontrib><creatorcontrib>Landete, Lamberto</creatorcontrib><creatorcontrib>Frederiksen, Jette</creatorcontrib><creatorcontrib>Bsteh, Gabriel</creatorcontrib><creatorcontrib>Mulero, Patricia</creatorcontrib><creatorcontrib>Comabella, Manuel</creatorcontrib><creatorcontrib>Hernández, Miguel A</creatorcontrib><creatorcontrib>Espiño, Mercedes</creatorcontrib><creatorcontrib>Prieto, José M</creatorcontrib><creatorcontrib>Pérez, Domingo</creatorcontrib><creatorcontrib>Otano, María</creatorcontrib><creatorcontrib>Padilla, Francisco</creatorcontrib><creatorcontrib>García-Merino, Juan A</creatorcontrib><creatorcontrib>Navarro, Laura</creatorcontrib><creatorcontrib>Muriel, Alfonso</creatorcontrib><creatorcontrib>Frossard, Lucienne Costa</creatorcontrib><creatorcontrib>Villar, Luisa M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Toboso, Inmaculada</au><au>Tejeda-Velarde, Amalia</au><au>Alvarez-Lafuente, Roberto</au><au>Arroyo, Rafael</au><au>Hegen, Harald</au><au>Deisenhammer, Florian</au><au>Sainz de la Maza, Susana</au><au>Alvarez-Cermeño, José C</au><au>Izquierdo, Guillermo</au><au>Paramo, Dolores</au><au>Oliva, Pedro</au><au>Casanova, Bonaventura</au><au>Agüera-Morales, Eduardo</au><au>Franciotta, Diego</au><au>Gastaldi, Matteo</au><au>Fernández, Oscar</au><au>Urbaneja, Patricia</au><au>Garcia-Dominguez, José M</au><au>Romero, Fernando</au><au>Laroni, Alicia</au><au>Uccelli, Antonio</au><au>Perez-Sempere, Angel</au><au>Saiz, Albert</au><au>Blanco, Yolanda</au><au>Galimberti, Daniela</au><au>Scarpini, Elio</au><au>Espejo, Carmen</au><au>Montalban, Xavier</au><au>Rasche, Ludwig</au><au>Paul, Friedemann</au><au>González, Inés</au><au>Álvarez, Elena</au><au>Ramo, Cristina</au><au>Caminero, Ana B</au><au>Aladro, Yolanda</au><au>Calles, Carmen</au><au>Eguía, Pablo</au><au>Belenguer-Benavides, Antonio</au><au>Ramió-Torrentà, Lluis</au><au>Quintana, Ester</au><au>Martínez-Rodríguez, José E</au><au>Oterino, Agustín</au><au>López de Silanes, Carlos</au><au>Casanova, Luis I</au><au>Landete, Lamberto</au><au>Frederiksen, Jette</au><au>Bsteh, Gabriel</au><au>Mulero, Patricia</au><au>Comabella, Manuel</au><au>Hernández, Miguel A</au><au>Espiño, Mercedes</au><au>Prieto, José M</au><au>Pérez, Domingo</au><au>Otano, María</au><au>Padilla, Francisco</au><au>García-Merino, Juan A</au><au>Navarro, Laura</au><au>Muriel, Alfonso</au><au>Frossard, Lucienne Costa</au><au>Villar, Luisa M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab</atitle><jtitle>Frontiers in neurology</jtitle><addtitle>Front Neurol</addtitle><date>2020-12-17</date><risdate>2020</risdate><volume>11</volume><spage>579438</spage><epage>579438</epage><pages>579438-579438</pages><issn>1664-2295</issn><eissn>1664-2295</eissn><abstract>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. 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 &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;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 &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. 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.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>33408681</pmid><doi>10.3389/fneur.2020.579438</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1664-2295
ispartof Frontiers in neurology, 2020-12, Vol.11, p.579438-579438
issn 1664-2295
1664-2295
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_c82f6fa684d240fe86a6b469a1788aa1
source PubMed Central Free
subjects biomarkers
demyelinating diseases
disease modifying treatments
multiple sclerosis
natalizumab
Neurology
progressive multifocal leucoencephalopathy
title New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T14%3A50%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20Algorithms%20Improving%20PML%20Risk%20Stratification%20in%20MS%20Patients%20Treated%20With%20Natalizumab&rft.jtitle=Frontiers%20in%20neurology&rft.au=Toboso,%20Inmaculada&rft.date=2020-12-17&rft.volume=11&rft.spage=579438&rft.epage=579438&rft.pages=579438-579438&rft.issn=1664-2295&rft.eissn=1664-2295&rft_id=info:doi/10.3389/fneur.2020.579438&rft_dat=%3Cproquest_doaj_%3E2476127527%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c465t-4168fbd8b57aad24f32ca771b841bcbdd9c3d445e248f026ada36cd3814810a43%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2476127527&rft_id=info:pmid/33408681&rfr_iscdi=true