New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab
Toboso, Inmaculada (Hospital Universitario Ramón y Cajal (Madrid))
Tejeda-Velarde, Amalia (Hospital Universitario Ramón y Cajal (Madrid))
Alvarez-Lafuente, Roberto (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Arroyo, Rafael (Hospital Universitario Quiron Salud)
Hegen, Harald (Medical University of Innsbruck)
Deisenhammer, Florian (Medical University of Innsbruck)
Sainz de la Maza, Susana (Hospital Universitario Ramón y Cajal (Madrid))
Alvarez-Cermeño, José C. (Hospital Universitario Ramón y Cajal (Madrid))
Izquierdo, Guillermo (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Paramo, Dolores (Hospital Universitario Virgen Macarena (Sevilla, Andalusia))
Oliva, Pedro (Hospital Universitario Central de Asturias)
Casanova, Bonaventura (Hospital Universitari i Politècnic La Fe (València))
Agüera-Morales, Eduardo (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Franciotta, Diego (Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation)
Gastaldi, Matteo (Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation)
Fernández, Oscar (Hospital Regional Universitario de Málaga)
Urbaneja, Patricia (Hospital Regional Universitario de Málaga)
Garcia-Dominguez, José M. (Hospital General Universitario Gregorio Marañón)
Romero, Fernando (Hospital General Universitario Gregorio Marañón)
Laroni, Alicia (University of Genoa, Ospedale Policlinico San Martino)
Uccelli, Antonio (University of Genoa, Ospedale Policlinico San Martino)
Perez-Sempere, Angel (Hospital General Universitario de Alicante (Alacant, País Valencià))
Saiz, Albert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Blanco, Yolanda (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Galimberti, Daniela (University of Milan)
Scarpini, Elio (University of Milan)
Espejo, Carmen (Hospital Universitari Vall d'Hebron)
Montalban, Xavier (Hospital Universitari Vall d'Hebron)
Rasche, Ludwig (Humboldt-Universität zu Berlin)
Paul, Friedemann (Charité - Universitätsmedizin Berlin)
González, Inés (Hospital Álvaro Cunqueiro (Vigo))
Álvarez, Elena (Hospital Álvaro Cunqueiro (Vigo))
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Caminero, Ana B. (Hospital Nuestra Señora de Sonsoles (Àvila))
Aladro, Yolanda (Hospital Universitario Getafe)
Calles, Carmen (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Eguía, Pablo (Hospital Doctor Jose Molina Orosa)
Belenguer-Benavides, Antonio (Consorci Hospitalari Provincial de Castelló)
Ramió-Torrentà, Lluís (Hospital Universitari de Girona Doctor Josep Trueta)
Quintana, Ester (Hospital Universitari de Girona Doctor Josep Trueta)
Martínez-Rodríguez, José E. (Hospital del Mar (Barcelona, Catalunya))
Oterino, Agustín (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
López de Silanes, Carlos (Hospital Universitario de Torrejón)
Casanova, Luis I. (Hospital Universitario de Torrejón)
Landete Pascual, Lamberto (Hospital Universitari Doctor Peset (València))
Frederiksen, Jette (Glostrup University Hospital Copenhagen)
Bsteh, Gabriel (Medical University of Innsbruck)
Mulero, P. (Hospital Universitari Vall d'Hebron)
Comabella, Manuel (Hospital Universitari Vall d'Hebron)
Hernández, Miguel A. (Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife))
Espiño, Mercedes (Hospital Universitario Ramón y Cajal (Madrid))
Prieto, José M. (Hospital Clínico Universitario (Santiago de Compostela, Galícia))
Pérez, Domingo (Hospital del Bierzo (Ponferrada, Lleó))
Otano, María (Complejo Hospitalario de Navarra)
Padilla, Francisco (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
García-Merino, Juan A. (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Navarro Cantó, Laura (Hospital General Universitario de Elche)
Muriel, Alfonso (Hospital Universitario Ramón y Cajal (Madrid))
Frossard, Lucienne Costa (Hospital Universitario Ramón y Cajal (Madrid))
Villar, Luisa M. (Hospital Universitario Ramón y Cajal (Madrid))
Universitat Autònoma de Barcelona

Date:	2020
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.
Grants:	Instituto de Salud Carlos III PI15/00513 Instituto de Salud Carlos III PI18/00572 Instituto de Salud Carlos III RD17/0015
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Multiple sclerosis ; Demyelinating diseases ; Biomarkers ; Natalizumab ; Progressive multifocal leucoencephalopathy ; Disease modifying treatments
Published in:	Frontiers in neurology, Vol. 11 (december 2020) , ISSN 1664-2295

DOI: 10.3389/fneur.2020.579438
PMID: 33408681

11 p, 5.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles