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

• Main Authors: Inmaculada Toboso, Amalia Tejeda-Velarde, Roberto Alvarez-Lafuente, Rafael Arroyo, Harald Hegen, Florian Deisenhammer, Susana Sainz de la Maza, José C. Alvarez-Cermeño, Guillermo Izquierdo, Dolores Paramo, Pedro Oliva, Bonaventura Casanova, Eduardo Agüera-Morales, Diego Franciotta, Matteo Gastaldi, Oscar Fernández, Patricia Urbaneja, José M. Garcia-Dominguez, Fernando Romero, Alicia Laroni, Antonio Uccelli, Angel Perez-Sempere, Albert Saiz, Yolanda Blanco, Daniela Galimberti, Elio Scarpini, Carmen Espejo, Xavier Montalban, Ludwig Rasche, Friedemann Paul, Inés González, Elena Álvarez, Cristina Ramo, Ana B. Caminero, Yolanda Aladro, Carmen Calles, Pablo Eguía, Antonio Belenguer-Benavides, Lluis Ramió-Torrentà, Ester Quintana, José E. Martínez-Rodríguez, Agustín Oterino, Carlos López de Silanes, Luis I. Casanova, Lamberto Landete, Jette Frederiksen, Gabriel Bsteh, Patricia Mulero, Manuel Comabella, Miguel A. Hernández, Mercedes Espiño, José M. Prieto, Domingo Pérez, María Otano, Francisco Padilla, Juan A. García-Merino, Laura Navarro, Alfonso Muriel, Lucienne Costa Frossard, Luisa M. Villar
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-12-01
• Series: Frontiers in Neurology
• Subjects: multiple sclerosis; demyelinating diseases; biomarkers; natalizumab; progressive multifocal leucoencephalopathy; disease modifying treatments
• Online Access: https://www.frontiersin.org/articles/10.3389/fneur.2020.579438/full

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.