title: Assessment of JC virus DNA in blood and urine from natalizumab-treated patients.
abstract: Analyses were conducted to determine the clinical utility of measuring JC virus (JCV) DNA in blood or urine of natalizumab-treated multiple sclerosis (MS) patients to predict the risk of progressive multifocal leukoencephalopathy (PML).
  
  
  
  A total of 12,850 blood and urine samples from nearly 1,400 patients participating in natalizumab clinical trials were tested for JCV DNA using a commercially available quantitative polymerase chain reaction (qPCR) assay. A subset of these samples was also tested using a more sensitive qPCR assay developed at the National Institutes of Health (NIH).
  
  
  
  At the time natalizumab dosing was suspended, JCV DNA was detected in plasma by the commercial assay in 4 of 1,397 (0.3%) patients; the NIH assay confirmed these positive samples and detected JCV DNA in an additional 2 of 205 (1%) patients who tested negative with the commercial assay. None of these 6 JCV DNA positive patients developed PML. In a 48-week study testing the safety of natalizumab redosing, JCV DNA was detected in plasma of 6 of 1,094 (0.3%) patients, none of whom developed PML. Urine at baseline and week 48 was assessed in 224 patients; 58 (26%) were positive at baseline, and 55 (25%) were positive after 48 weeks of natalizumab, treatment. JCV DNA was not detected in peripheral blood mononuclear cells from any of these 1,094 patients before or after natalizumab treatment. In 5 patients who developed PML, JCV DNA was not detected in blood at any time point before symptoms first occurred.
  
  
  
  Measuring JCV DNA in blood or urine with currently available methods is unlikely to be useful for predicting PML risk in natalizumab-treated MS patients.
authors.affiliation: Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. rudickr@ccf.org
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Connor
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Goodman
authors.forename: Soma S
authors.initials: SS
authors.lastname: Ray
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Griffith
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Jurgensen
authors.forename: Leonid
authors.initials: L
authors.lastname: Gorelik
authors.forename: Fiona
authors.initials: F
authors.lastname: Forrestal
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Sandrock
authors.forename: Susan E
authors.initials: SE
authors.lastname: Goelz
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral / Q000097:blood / Q000627:therapeutic use / Q000652:urine; D016001:Confidence Intervals; D004279:DNA, Viral / Q000097:blood / Q000276:immunology* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000628:therapy / Q000652:urine; D008297:Male; D000069442:Natalizumab; D018709:Statistics, Nonparametric
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D004279:DNA, Viral; D000069442:Natalizumab