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Assessment of JC virus DNA in blood and urine from natalizumab-treated patients

Ann Neurol. 2010 Sep;68(3):304-10. doi: 10.1002/ana.22107.

Abstract

Objective: 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).

Methods: 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).

Results: 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.

Interpretation: 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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / therapeutic use
  • Antibodies, Viral* / urine
  • Confidence Intervals
  • DNA, Viral / blood
  • DNA, Viral / immunology*
  • DNA, Viral / urine
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Follow-Up Studies
  • Humans
  • JC Virus / immunology*
  • Leukoencephalopathy, Progressive Multifocal* / blood
  • Leukoencephalopathy, Progressive Multifocal* / therapy
  • Leukoencephalopathy, Progressive Multifocal* / urine
  • Male
  • Natalizumab
  • Statistics, Nonparametric

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • DNA, Viral
  • Natalizumab