Original Article

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

  1. Richard A. Rudick MD1,*,
  2. Paul W. O'Connor MD2,
  3. Chris H. Polman MD3,
  4. Andrew D. Goodman MD4,
  5. Soma S. Ray PhD5,
  6. Nancy M. Griffith PhD5,
  7. Stephanie A. Jurgensen BS, MPH5,
  8. Leonid Gorelik PhD5,
  9. Fiona Forrestal MSc5,
  10. Alfred W. Sandrock MD, PhD5,
  11. Susan E. Goelz PhD5

Article first published online: 24 AUG 2010

DOI: 10.1002/ana.22107

Issue

Annals of Neurology

Annals of Neurology

Volume 68, Issue 3, pages 304–310, September 2010

Additional Information

How to Cite

Rudick, R. A., O'Connor, P. W., Polman, C. H., Goodman, A. D., Ray, S. S., Griffith, N. M., Jurgensen, S. A., Gorelik, L., Forrestal, F., Sandrock, A. W. and E. Goelz, S. (2010), Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol., 68: 304–310. doi: 10.1002/ana.22107

Author Information

  1. 1

    Cleveland Clinic Foundation, Cleveland, OH

  2. 2

    St. Michael's Hospital, Toronto, Ontario, Canada

  3. 3

    VU Medical Center, Free University Hospital, Amsterdam, the Netherlands

  4. 4

    University of Rochester Medical Center, Rochester, NY

  5. 5

    Biogen Idec, Inc., Cambridge, MA

*Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, the Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195

Publication History

  1. Issue published online: 30 AUG 2010
  2. Article first published online: 24 AUG 2010
  3. Manuscript Accepted: 28 MAY 2010
  4. Manuscript Revised: 6 MAY 2010
  5. Manuscript Received: 19 MAR 2010

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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. Ann Neurol 2010

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