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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • 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
  • 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
  • Villar LM

Grupos

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.

Datos de la publicación

ISSN/ISSNe:
1664-2295, 1664-2295

Frontiers in neurology  FRONTIERS MEDIA SA

Tipo:
Article
Páginas:
579438-579438
PubMed:
33408681
Factor de Impacto:
1,230 SCImago ℠
Cuartil:
Q2 SCImago ℠

Citas Recibidas en Web of Science: 6

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Keywords

  • biomarkers, demyelinating diseases, disease modifying treatments, multiple sclerosis, natalizumab, progressive multifocal leucoencephalopathy

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