Toboso, InmaculadaTejeda-Velarde, AmaliaAlvarez-Lafuente, RobertoArroyo, RafaelHegen, HaraldDeisenhammer, FlorianSainz de la Maza, SusanaAlvarez-Cermeño, José CIzquierdo, GuillermoParamo, DoloresOliva, PedroCasanova, BonaventuraAgüera-Morales, EduardoFranciotta, DiegoGastaldi, MatteoFernández, OscarUrbaneja, PatriciaGarcia-Dominguez, José MRomero, FernandoLaroni, AliciaUccelli, AntonioPerez-Sempere, AngelSaiz, AlbertBlanco, YolandaGalimberti, DanielaScarpini, ElioEspejo, CarmenMontalban, XavierRasche, LudwigPaul, FriedemannGonzález, InésÁlvarez, ElenaRamo, CristinaCaminero, Ana BAladro, YolandaCalles, CarmenEguía, PabloBelenguer-Benavides, AntonioRamió-Torrentà, LluisQuintana, EsterMartínez-Rodríguez, José EOterino, AgustínLópez de Silanes, CarlosCasanova, Luis ILandete, LambertoFrederiksen, JetteBsteh, GabrielMulero, PatriciaComabella, ManuelHernández, Miguel AEspiño, MercedesPrieto, José MPérez, DomingoOtano, MaríaPadilla, FranciscoGarcía-Merino, Juan ANavarro, LauraMuriel, AlfonsoFrossard, Lucienne CostaVillar, Luisa M2023-02-092023-02-092020-12-171664-2295http://hdl.handle.net/10668/16933Overview: 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 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 fromenAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/biomarkersdemyelinating diseasesdisease modifying treatmentsmultiple sclerosisnatalizumabprogressive multifocal leucoencephalopathyresearch article33408681open access10.3389/fneur.2020.579438PMC7780851https://www.frontiersin.org/articles/10.3389/fneur.2020.579438/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780851/pdf