New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab
Por:
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 and Villar LM
Publicada:
17 dic 2020
Ahead of Print:
17 dic 2020
Resumen:
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.
Filiaciones:
Toboso I:
Immunology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Tejeda-Velarde A:
Immunology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Alvarez-Lafuente R:
Instituto de Investigación Sanitaria San Carlos (IDISSC), Hospital Clinico San Carlos, Madrid, Spain
Arroyo R:
Department of Neurology, Hospital Universitario Quiron Salud, Madrid, Spain
Hegen H:
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Deisenhammer F:
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Sainz de la Maza S:
Neurology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Alvarez-Cermeño JC:
Neurology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Izquierdo G:
Neurology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain
Paramo D:
Neurology Department, Hospital Universitario Virgen Macarena, Sevilla, Spain
Oliva P:
Neurology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
Casanova B:
Neurology Department, Hospital Universitario la Fe, Valencia, Spain
Agüera-Morales E:
Neurology Department, Hospital Universitario Reina Sofia, Cordoba, Spain
Franciotta D:
Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy
Gastaldi M:
Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy
Fernández O:
Neurology Department, Hospital Regional Universitario, Malaga, Spain
Urbaneja P:
Neurology Department, Hospital Regional Universitario, Malaga, Spain
Garcia-Dominguez JM:
Neurology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Romero F:
Neurology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Laroni A:
University of Genoa, Ospedale Policlinico San Martino, Genoa, Italy
Uccelli A:
University of Genoa, Ospedale Policlinico San Martino, Genoa, Italy
Perez-Sempere A:
Neurology Department, Hospital General Universitario de Alicante, Alicante, Spain
Saiz A:
Neurology Service, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
Blanco Y:
Neurology Service, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
Galimberti D:
Centro Dino Ferrari, Fondazione Ca' Granda, Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico, University of Milan, Milan, Italy
Scarpini E:
Centro Dino Ferrari, Fondazione Ca' Granda, Istituti di Recovero e Cura a Carattere Scientifico (IRCCS) Ospedale Policlinico, University of Milan, Milan, Italy
Espejo C:
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Montalban X:
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Rasche L:
Department of Neurology, NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Paul F:
Department of Neurology, NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine, Berlin, Germany
González I:
Neurology Department, Hospital Álvaro Cunqueiro, Vigo, Spain
Álvarez E:
Neurology Department, Hospital Álvaro Cunqueiro, Vigo, Spain
Ramo C:
Neurology Department, Hospital Germans Trias i Pujol, Badalona, Spain
Caminero AB:
Neurology Department, Hospital Nuestra Señora de Sonsoles, Avila, Spain
Aladro Y:
Neurology Department, Hospital Universitario Getafe, Getafe, Spain
Calles C:
Neurology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain
Eguía P:
Neurology Department, Hospital Doctor Jose Molina Orosa, Arrecife, Spain
:
Neurology Department, Hospital General Universitario de Castellón, Castellón, Spain
Ramió-Torrentà L:
Neurology Department, Hospital Universitario Doctor Josep Trueta, Girona, Spain
Quintana E:
Neurology Department, Hospital Universitario Doctor Josep Trueta, Girona, Spain
Martínez-Rodríguez JE:
Neurology Department, Hospital del Mar, Barcelona, Spain
Oterino A:
Neurology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
López de Silanes C:
Neurology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Spain
Casanova LI:
Neurology Department, Hospital Universitario de Torrejón, Torrejón de Ardoz, Spain
:
Neurology Department, Hospital Universitario Dr. Peset, Valencia, Spain
Frederiksen J:
Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark
Bsteh G:
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
Mulero P:
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Comabella M:
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Hernández MA:
Neurology Department, Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain
Espiño M:
Immunology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Prieto JM:
Neurology Department, Hospital Clínico de Santiago, Santiago de Compostela, Spain
Pérez D:
Neurology Department, Hospital del Bierzo, Ponferrada, Spain
Otano M:
Neurology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
Padilla F:
Neurology Department, Hospital Clinico de Malaga, Malaga, Spain
García-Merino JA:
Neurology Department, Hospital Puerta de Hierro, Majadahonda, Madrid, Spain
:
Neurology Department, Hospital General de Elche, Elche, Spain
Muriel A:
Biostatistics Unit, Hospital Univesitario Ramon y Cajal, Instituto Ramon y Cajal para la Investigación Sanitaria (IRYCIS), Madrid, Spain
Frossard LC:
Neurology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Villar LM:
Immunology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain
Green Published, Green Accepted, gold
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