title: Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy.
abstract: OBJECTIVE
  The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti-JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients.
  
  
  METHODS
  The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody-positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated.
  
  
  RESULTS
  Anti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody-positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time.
  
  
  CONCLUSIONS
  Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody-positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted.
authors.affiliation: Biogen Idec, Cambridge, MA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Plavina
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
authors.forename: Gary
authors.initials: G
authors.lastname: Bloomgren
authors.forename: Sandra
authors.initials: S
authors.lastname: Richman
authors.forename: Amy
authors.initials: A
authors.lastname: Pace
authors.forename: Sophia
authors.initials: S
authors.lastname: Lee
authors.forename: Brian
authors.initials: B
authors.lastname: Schlain
authors.forename: Denise
authors.initials: D
authors.lastname: Campagnolo
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.forename: Barry
authors.initials: B
authors.lastname: Ticho
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006801:Humans; D007577:JC Virus / Q000378:metabolism*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood* / Q000139:chemically induced / Q000175:diagnosis*; D008137:Longitudinal Studies; D000069442:Natalizumab; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D015415:Biomarkers; D000069442:Natalizumab