Helmholtz Gemeinschaft


New algorithms improving PML risk stratification in MS patients treated with natalizumab

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Item Type:Article
Title:New algorithms improving PML risk stratification in MS patients treated with natalizumab
Creators Name:Toboso, I. and Tejeda-Velarde, A. and Alvarez-Lafuente, R. and Arroyo, R. and Hegen, H. and Deisenhammer, F. and Sainz de la Maza, S. and Alvarez-Cermeño, J.C. and Izquierdo, G. and Paramo, D. and Oliva, P. and Casanova, B. and Agüera-Morales, E. and Franciotta, D. and Gastaldi, M. and Fernández, O. and Urbaneja, P. and Garcia-Dominguez, J.M. and Romero, F. and Laroni, A. and Uccelli, A. and Perez-Sempere, A. and Saiz, A. and Blanco, Y. and Galimberti, D. and Scarpini, E. and Espejo, C. and Montalban, X. and Rasche, L. and Paul, F. and González, I. and Álvarez, E. and Ramo, C. and Caminero, A.B. and Aladro, Y. and Calles, C. and Eguía, P. and Belenguer-Benavides, A. and Ramió-Torrentà, L. and Quintana, E. and Martínez-Rodríguez, J.E. and Oterino, A. and López de Silanes, C. and Casanova, L.I. and Landete, L. and Frederiksen, J. and Bsteh, G. and Mulero, P. and Comabella, M. and Hernández, M.A. and Espiño, M. and Prieto, J.M. and Pérez, D. and Otano, M. and Padilla, F. and García-Merino, J.A. and Navarro, L. and Muriel, A. and Frossard, L.C. and Villar, L.M.
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:Multiple Sclerosis, Demyelinating Diseases, Biomarkers, Natalizumab, Progressive Multifocal Leucoencephalopathy, Disease Modifying Treatments
Source:Frontiers in Neurology
Publisher:Frontiers Media SA
Page Range:579438
Date:17 December 2020
Official Publication:https://doi.org/10.3389/fneur.2020.579438
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library