Late breaking newsFriday, September 11, 2009, 15:30 - 17:00Evaluation of natalizumab treatment on the presence of JC virus in blood and urine from multiple sclerosis patientsR.A. Rudick, C.H. Polman, P.W. O’Connor, A.D. Goodman, S. Ray, C. Ryschkewitsch, S. Jurgensen, S. Goelz, F. Forrestal, L. Gorelik, M.A. Panzara, A.W. Sandrock, E.O. Major (Cleveland, US; Amsterdam, NL; Toronto, CA; Rochester, Cambridge, Bethesda, US)
Background: Natalizumab is associated with a risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by JC virus (JCV). We evaluated to what extent natalizumab affects systemic presence of JCV in multiple sclerosis patients.
Methods: Plasma, serum, PBMCs, and urine samples from both the natalizumab safety evaluation and Safety of TYSABRI Re-dosing and Treatment (STRATA) studies were analyzed for the presence of JCV DNA. JCV DNA was assessed by quantitative polymerase chain reaction using a commercial assay (ViraCor) with levels of sensitivity at 500 copies/mL as a limit of quantitation and 50 copies/mL as a limit of detection and a more sensitive assay from the National Institutes of Health (NIH) with levels of sensitivity at 10 copies/mL.
Results: In STRATA, 1094 patients were serially monitored over 48 weeks for JCV DNA using the ViraCor assay. There was no discernable difference in JCV presence pre-natalizumab treatment and 48 wks post treatment in plasma with an overall incidence of <1% (1/1078 at baseline and 2/675 at wk 48). No JCV was detected in any of the 4066 STRATA PBMC samples (baseline: 0/1069; 48 weeks: 0/695) using the ViraCor assay. There also was no substantial change in the percentage of patients with JCV DNA (nor viral load) detected in urine over 48 weeks of treatment with natalizumab with JCV detected in 25-26% of urine samples (overall: 59/223, baseline 58/223; 48 weeks 55/223), a percentage comparable to other population surveys. In the safety evaluation study, JCV DNA was detected in plasma in 4 of 1397 (<1%) patients (mean natalizumab exposure of 22 months) using the ViraCor assay. This value is consistent with published results in healthy controls and with the incidence in untreated MS patients from the STRATA study where the ViraCor assay was also used. A subset of 205 plasma samples from this study was retested using the NIH assay; an additional 2 (~1%) patients had JCV DNA detected. Of the 6 patients with JCV DNA detected in plasma, 3 patients were natalizumab naïve and viral DNA detection in the other 3 patients was at 8, 28, and 35 doses. To date, no patient with detectable JCV in plasma who continued natalizumab has developed PML.
Conclusions: In the large group of MS patients evaluated, there appears to be no substantial change in the presence of JCV DNA in plasma, PBMCs, and urine with natalizumab treatment.
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