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February 2016; 3 (1) ArticleOpen Access

Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values

Nicholas Schwab, Tilman Schneider-Hohendorf, Béatrice Pignolet, Johanna Breuer, Catharina C. Gross, Kerstin Göbel, David Brassat, Heinz Wiendl
First published January 27, 2016, DOI: https://doi.org/10.1212/NXI.0000000000000195
Nicholas Schwab
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Tilman Schneider-Hohendorf
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Béatrice Pignolet
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Johanna Breuer
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Catharina C. Gross
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Kerstin Göbel
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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David Brassat
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Heinz Wiendl
From the Department of Neurology (N.S., T.S.-H., J.B., C.C.G., K.G., H.W.), University of Münster, Germany; and Pole des Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 et Université de Toulouse, UPS, Toulouse, France. D.B. also represents the BioNAT Study Group.
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Citation
Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values
Nicholas Schwab, Tilman Schneider-Hohendorf, Béatrice Pignolet, Johanna Breuer, Catharina C. Gross, Kerstin Göbel, David Brassat, Heinz Wiendl
Neurol Neuroimmunol Neuroinflamm Feb 2016, 3 (1) e195; DOI: 10.1212/NXI.0000000000000195

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Abstract

Objective: The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment.

Methods: German (n = 1,921; 525 longitudinally) and French (n = 1,259; 711 longitudinally) patients were assessed for JCV serology alongside their therapy with natalizumab.

Results: JCV serostatus changed in 69 of 525 longitudinally followed German patients (13.1%) over 14.8 months. Seroconversion according to serostatus was seen in 43 of 339 initially JCV− German patients (12.7% in 14.8 months; 10.3% per year) and 41 of 243 initially JCV− French patients (16.9% in 24 months; 8.5% per year). JCV index values could be reproduced (R2 = 0.89) with the caveat of 8 of 50 samples (16%) being set into different risk categories between 2 assessments. Index values of JCV+ patients rose over time (p = 0.009) but not because of aging. Treatment with natalizumab was associated with a 15.9% increase of value in JCV+ patients in 14.8 months (12.9% per year).

Conclusions: JCV seroconversion and index values may be influenced by treatment with natalizumab. It is therefore important to monitor patients' JCV serology but also to incorporate additional risk factors into the progressive multifocal leukoencephalopathy risk stratification.

GLOSSARY

JCV=
John Cunningham virus;
MS=
multiple sclerosis;
PML=
progressive multifocal leukoencephalopathy;
RRMS=
relapsing-remitting multiple sclerosis

Footnotes

  • ↵* These authors contributed equally to this work.

  • Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was paid by the University of Münster.

  • BioNAT Study Group coinvestigators are listed at Neurology.org/nn.

  • See editorial

  • Supplemental data at Neurology.org/nn

  • Received July 29, 2015.
  • Accepted in final form November 10, 2015.
  • © 2016 American Academy of Neurology

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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Letters: Rapid online correspondence

  • Re:Time to audit all reported PML cases
    • Nicholas Schwab, Assistant Professor, Department of Neurology, University of Muenster, Germany.nicholas.schwab@ukmuenster.de
    • T. Schneider-Hohendorf; H. Wiendl;
    Submitted February 22, 2016
  • Time to audit all reported PML cases
    • Jagannadha Avasarala, Associate Professor of Neurology, Greenville Health System & U of South Carolina School of Medicinejavasarala@ghs.org
    Submitted February 16, 2016
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