AUTHOR=Toboso Inmaculada , Tejeda-Velarde Amalia , Alvarez-Lafuente Roberto , Arroyo Rafael , Hegen Harald , Deisenhammer Florian , Sainz de la Maza Susana , Alvarez-Cermeño José C. , Izquierdo Guillermo , Paramo Dolores , Oliva Pedro , Casanova Bonaventura , Agüera-Morales Eduardo , Franciotta Diego , Gastaldi Matteo , Fernández Oscar , Urbaneja Patricia , Garcia-Dominguez José M. , Romero Fernando , Laroni Alicia , Uccelli Antonio , Perez-Sempere Angel , Saiz Albert , Blanco Yolanda , Galimberti Daniela , Scarpini Elio , Espejo Carmen , Montalban Xavier , Rasche Ludwig , Paul Friedemann , González Inés , Álvarez Elena , Ramo Cristina , Caminero Ana B. , Aladro Yolanda , Calles Carmen , Eguía Pablo , Belenguer-Benavides Antonio , Ramió-Torrentà Lluis , Quintana Ester , Martínez-Rodríguez José E. , Oterino Agustín , López de Silanes Carlos , Casanova Luis I. , Landete Lamberto , Frederiksen Jette , Bsteh Gabriel , Mulero Patricia , Comabella Manuel , Hernández Miguel A. , Espiño Mercedes , Prieto José M. , Pérez Domingo , Otano María , Padilla Francisco , García-Merino Juan A. , Navarro Laura , Muriel Alfonso , Frossard Lucienne Costa , Villar Luisa M. 

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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.579438

DOI=10.3389/fneur.2020.579438

ISSN=1664-2295

ABSTRACT=Background: The use of Natalizumab is limited in MS by the risk of progressive multifocal leucoencephalopathy (PML). The factors currently used to stratify PML risk present some limitations.
Objective: To identify new risk factors that improve the PML risk stratification.
Methods: We studied 1307 MS patients treated with natalizumab for a median time of 3.28 year. Factors associated with PML onset were explored by uni- and multivariate logistic regression.
Results: The multivariate analysis of total cohort identified anti-JC virus antibody indices (OR=18.07) and relapse rate (OR=4.66) as the best predictors for the onset of PML. The risk ranged from < 1/3300 to 1/50 depending on these variables. 
In the 277 patients with lipid-specific oligoclonal IgM bands restricted to CSF (LS-OCMB) assessment, age at natalizumab onset, anti-JCV antibody indices, and LS-OCMB status predicted PML risk (AUC=0.92). The absence of LS-OCMB was the best individual predictor (OR=26.83). Age was also an important factor (OR=6.74), which contributed to PML risk similarly to anti JC status (OR=6.52). Depending of these three factors the individual risk ranged from <1/10000 to 1/33. 
Conclusion: Disease activity, LS-OCMB antibody levels and age can help tailor natalizumab therapy in MS patients, as predictors of PML