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May 16, 2012
Letter to the Editor

Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort

A.K. Trampe, MSc, C. Hemmelmann, PhD, A. Stroet, MD, A. Haghikia, MD, K. Hellwig, MD, H. Wiendl, MD, S. Goelz, PhD, A. Ziegler, MD, R. Gold, MD, and A. Chan, MDAuthors Info & Affiliations
May 29, 2012 issue
78 (22) 1736-1742
https://doi.org/10.1212/WNL.0b013e3182583022
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Abstract

Objective:

To investigate the rate of seropositivity of anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab in the postmarketing setting and to assess anti-JCV serostatus in samples obtained before diagnosis of progressive multifocal leukoencephalopathy (PML).

Methods:

This was a blinded, retrospective cross-sectional and longitudinal analysis for anti-JCV antibodies using a confirmatory 2-step ELISA on 2,782 blood samples obtained from 2,253 patients nationwide for routine testing for anti-natalizumab antibodies during open-label treatment between 2007 and 2010.

Results:

Of the natalizumab-treated patients with MS, 58.8% tested positive for anti-JCV antibodies. The rate of seropositivity was higher in males and increased with age, with a plateau between age intervals 20–29 and 30–39 years. In longitudinal analyses, 19 of 194 (9.8%) patients converted from anti-JCV antibody-negative to seropositive status over 7.7 months; 4.7% reverted from antibody-positive to seronegative status over 7.9 months. Antibody levels, especially in the latter group, were low, indicating fluctuations around the lower cut point of the assay. Neither anti-JCV serostatus nor antibody levels were associated with immunosuppressive pretreatment, duration of natalizumab treatment, or anti-natalizumab antibodies. All samples obtained from 10 patients who developed PML were seropositive (13 samples before PML diagnosis [2.0–37.6 months]; 2 samples at diagnosis). Antibody levels in these samples were higher than those in samples from seropositive patients who did not develop PML.

Conclusions:

These data argue for the potential clinical utility of JCV serology for PML risk stratification. However, further investigations of fluctuations in serostatus and of antibody levels for a more precise understanding of the predictive value are warranted.

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Letters to the Editor
11 June 2012
Re:Comment on "Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort"
Anne-K. Trampe, M.Sc.
Anne-Kathrin Trampe, Bochum, Germany; Anke Stroet, Bochum, Germany; Ralf Gold, Bochum, Germany; Andrew Chan, Bochum, Germany

Dr. Zahednasab indicates that several studies have investigated JCV-DNA in urine as a potential tool for PML risk stratification. [1-3] In one of the largest studies[3], urinary JCV-DNA could not be detected in one of three patients who subsequently developed PML; urinary JCV-excretion was detected frequently and did not increase during natalizumab treatment. Thus, predictive values of either positive or negative tests appear to be low. [3] Using urinary JCV-DNA analysis a false negative rate of the 2-step anti JCV-antibody ELISA of approximately 2.7% can be calculated. [1] Due to lack of biomaterial we were not able to determine the rate of false negative findings of anti-JCV serology in our cohort. Given the current label of natalizumab in Germany, the majority of patients have undergone immunomodulatory pretreatment ( e.g., with IFN- beta). [4] Since we aimed to investigate the potential utility of anti-JCV serology in clinical practice, we did not exclude these patients from analysis. [5] Furthermore, our data do not indicate an immunomodulatory pretreatment effect on anti-JCV serostatus or titer (median normalized optical density (25%-75% percentile): untreated 0.542 (0.207- 1.080), n=59; immunmodulators: 0.579 (0.290-0.974), n=786, p=n.s.). [5] We agree that further investigations are needed to fully elucidate the predictive value of anti JCV-antibody testing in PML risk stratification.

1. Bozic C, Richman S, Plavina T, et al. Anti-John Cunnigham virus antibody prevalence in multiple sclerosis patients: Baseline results of STRATIFY-1. Annals of neurology 2011;70:713-721.

2. Laroni A, Giacomazzi CG, Grimaldi L, et al. Urinary JCV-DNA Testing during Natalizumab Treatment May Increase Accuracy of PML Risk Stratification. J Neuroimmune Pharmacol. 2012 May 16. [Epub ahead of print]

3. Rudick RA, O'Connor PW, Polman CH, et al. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Annals of neurology 2010;68:304-310.

4. Haghikia A, Fischer M, Hellwig K, et al. Open use of natalizumab. neuttralising antibodies and clinical data. Nervenarzt. 2008 Jun;79:716-9.

5. Trampe AK, Hemmelmann C, Stroet A, et al. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology 2012;78:1736-1742.

For disclosures, contact the editorial office at [email protected].
25 May 2012
Comment on "Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort"
Hamid Zahednasab, MSc student
no author listed

Trampe et al.[1] should be commended for their investigation into the rate of seropositivity of the anti-JC virus (JCV) antibodies in a German multiple sclerosis (MS) cohort treated with natalizumab. Further points need to be considered.

Trampe et al [1] investigated the rate of anti-JCV antibodies by using a confirmatory 2-step ELISA on 2,782 blood samples. Although the serum sample is a good option for the detection of anti-JCV antibodies by ELISA method, it would be more accurate if they measured JVC-DNA in the urine samples of MS patients. It has been shown that the subjects who developed PML in the longitudinal cohort had detectable JCV- DNA in urine at all time-points whereas serum or blood from PML patients were always negative before the onset of disease. [2] This same report also showed that four subjects with JCV-DNA in urine and undetectable anti-JCV antibodies were retested for anti-JCV antibodies and three out of four resulted positive. Thus, it would be more plausible that testing JCV-DNA in urine is complementary to testing anti-JCV antibodies to monitor patients at risk of PML.

Patients taking IFN-beta should be excluded from this study. It has been shown that the administration of IFN -beta can lead to the reduction of JCV genome [3] and may result in a false-negative due to decreasing the JCV titer.

1. Trampe AK, Hemmelmann C, Stroet A, et al. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology. 2012 May 16.

2. Laroni A, Giacomazzi CG, Grimaldi L, et al. Urinary JCV-DNA Testing during Natalizumab Treatment May Increase Accuracy of PML Risk Stratification. J Neuroimmune Pharmacol. 2012 May 16

3. Delbue S, Guerini FR, Mancuso R, et al. JC virus viremia in interferon- beta -treated and untreated Italian multiple sclerosis patients and healthy controls. J Neurovirol 2007; 13:73-77.

For disclosures, contact editorial office at [email protected].

Information & Authors

Information

Published In

Neurology®
Volume 78 • Number 22 • May 29, 2012
Pages: 1736-1742
PubMed: 22592369

Copyright

Copyright © 2012 by AAN Enterprises, Inc.

Publication History

Received: October 17, 2011
Accepted: January 25, 2012
Published online: May 16, 2012
Published in print: May 29, 2012

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Disclosure

A.K. Trampe and Dr. Hemmelmann report no disclosures. Dr. Stroet has received personal compensation for activities with Novartis. Dr. Haghikia has received limited research support from Biogen Idec and speaker honoraria from Bayer Healthcare, Biogen Idec, Teva, and Merck Serono. Dr. Hellwig had received research support and speaker honoraria from Biogen Idec, Bayer Schering, Teva-sanofi aventis, Merck Serono, and Novartis Pharma. Dr. Wiendl has received research support from the German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis”), Bayer Healthcare, Biogen Idec/Elan, sanofi-aventis, Schering-Plough Corp., EMD Serono, TEVA Neuroscience, Medac, Lundbeck Research USA Inc., and Novo Nordisk and personal compensation for activities with Bayer Healthcare, Biogen Idec/Elan, sanofi-aventis, Schering-Plough Corp., EMD Serono, TEVA Neuroscience, Medac, Lundbeck Research USA Inc., and Novo Nordisk as a speaker or consultant. Dr. Goelz was an employee of Biogen Idec and is an employee of Elan Pharmaceuticals and holds stock. Dr. Ziegler has received research support from the German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis”). Dr. Gold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, and Teva Neuroscience and in an editorial capacity from Therapeutic Advances in Neurological Disorders; patent payments from Biogen Idec, and research support from the German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis” [KKNMS], CONTROL MS, 01GI0914), Bayer Healthcare, Biogen Idec, Merck Serono, Teva Neuroscience, and Novartis. Dr. Chan has received personal compensation as a speaker or consultant for Bayer Schering, Biogen Idec, Merck Serono, Novartis, sanofi-aventis, and Teva Neuroscience and research support from the German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis” [KKNMS], CONTROL MS, 01GI0914), Bayer Schering, Biogen Idec, Merck Serono, and Novartis. Go to Neurology.org for full disclosures.

Authors

Affiliations & Disclosures

A.K. Trampe, MSc
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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C. Hemmelmann, PhD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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A. Stroet, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Novartis, speaker honoraria
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
A. Haghikia, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
I have received limited research support from Biogen Idec and speakers honoraria from Bayer Healthcare, Biogen Idec, Teva and Merck Serono.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Limited research support by Biogen Idec
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
K. Hellwig, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
Novartis Pharma Speakers’ Bureaus: Honoraria from Biogen, Bayer Helathcare, Teva, Sanofi, Merck and Novartis Pharma.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Biogen, Bayer Helathcare, Teva, Sanofi, Merck and Novartis Pharma.
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
H. Wiendl, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
H. Wiendl received honoraria for lecturing and travel expenses for attending meetings and received financial research support from Bayer, Biogen Idec/Elan, Sanofi- Aventis, Schering, Serono, and Teva Pharmaceuticals. H.W. has served or serves as consultant for Serono, Medac, Sanofi-Aventis/TEVA, Biogen Idec, BayerVital/Schering, NOvartis and NovoNordisk.)
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
H. Wiendl has received honoraria for lecturing and travel expenses for attending meetings and received financial research support from Bayer, Biogen Idec/Elan, Sanofi Aventis, Schering GmbH, MerckSerono, Teva, Novartis, Medac, Genzyme and NovoNordisk
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
- Support of research projects by pharmaceutical industry (Bayer, Biogen Idec/Elan, Sanofi Aventis, Schering GmbH, MerckSerono, Teva, Novartis, Medac, Genzyme and NovoNordisk)
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
S. Goelz, PhD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
prior employee with Biogen Idec 1988-2011 current employee with Elan pharmaceuticals 2011-present
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
prior employee with Biogen Idec 1988-2011 current employee with Elan pharmaceuticals 2011-present
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
I own stock in Biogen Idec and have stock options from Elan Pharmaceuticals
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
I own stock in Biogen Idec and have stock options from Elan Pharmaceuticals
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
A. Ziegler, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Protagen, IntegraGen
Research Support, Government Entities:
1.
2009-2016Phenomics, supported by German Ministry of Education and Research (0315536F) 2009-2014German Neonatal Network, supported by German Ministry of Education and Research (01ER0805) 2010-2013Integrative genomics and coronary diseases – from genome-wide mega studies to functional understanding, supported by BMBF (01KU0908A, 01KU0908B) 2011-2014Video-based training for rehabilitation of upper limb functions after stroke: A new treatment exploiting the mirror neuron system (Acronym: Videotherapie), supported by DFG (BI 486/2-1) 2009-2012Automatic evaluation of cluster plots (ABC-plots), supported by German Research Foundation (ZI 591/17-1) 2009-2012Clinical Competence Net Multiple Sclerosis: ControlMS, supported by German Ministry of Education and Research (01GI0916) 2011-2014BiomarCARE, supported by EU (HEALTH-2011-278913)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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R. Gold, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
TEVA three DSMB boards; BiogenIdec advisory boards; BayerSchering advisory boards; Novartis advisory boards
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
speaker at BiogenIdec symposia and satellites; speaker at TEVA symposia and satellites; speaker at BayerSchering symposia and satellites; speaker at Novartis symposia and satellites
Editorial Boards:
1.
Therapeutic Advances in Neurological Diseases, editor since 2008; Am J Path, editorial board since 2009; J Neuroimmunol, editorial board since 2006
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
for BiogenIdec, ELAN and TEVA
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
TEVA; BiogenIdec; BayerSchering; MerckSerono; Novartis
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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A. Chan, MD
From the Department of Neurology (A.K.T., A.S., A.H., K.H., R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Institut für Medizinische Biometrie und Statistik (C.H., A.Z.), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; Clinic for Neurology-Inflammatory Disorders of the Central Nervous System and Neurooncology (H.W.), University of Münster, Münster, Germany; and Elan Pharmaceuticals (S.G.), Dublin, Ireland.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Bayer Schering, speaker honoraria; Biogen Idec, speaker honoraria; Merck Serono, speaker honoraria; Sanofi-Aventis, speaker honoraria; Teva Neuroscience, speaker honoraria
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Bayer Schering, consultant; Biogen Idec, consultant; Merck Serono, consultant; Sanofi-Aventis, consultant; Teva Neuroscience, consultant
Speakers’ Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Bayer Schering; Biogen Idec; Merck Serono; Novartis
Research Support, Government Entities:
1.
German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis” (KKNMS), CONTROL MS), 01GI0914, 2009-2011
Research Support, Academic Entities:
1.
Ruhr University Bochum, Research support (FoRUM)
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
Sanofi-Aventis, 2010-2011, expert consultant, authoring of a clinical overview that was submitted to german regulatory authorities for approval of methylprednisolone in the treatment of Multiple Sclerosis
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Notes

Study funding: Supported in part by the German Bundesministerium für Bildung und Forschung (BMBF), German competence Network Multiple Sclerosis (KKNMS), natalizumab pharmacovigilance study no. 01GI0914. Biogen Idec provided financial support for shipment and analysis of samples.
Correspondence & reprint requests to Dr. Chan: [email protected]

Author Contributions

Study concept and design: Dr. Goelz, Dr. Gold, Dr. Chan. Acquisition of data: A.K. Trampe, Dr. Stroet, Dr. Haghikia, Dr. Hellwig, Dr. Wiendl. Analysis and interpretation of data: A.K. Trampe, Dr. Hemmelmann, Dr. Stroet, Dr. Ziegler, Dr. Gold, Dr. Chan. Statistical analysis: Dr. Hemmelmann, Dr. Ziegler, Dr. Chan. Drafting of manuscript: A.K. Trampe, Dr. Hemmelmann, Dr. Stroet, Dr. Goelz, Dr. Chan. Critical revision of the manuscript for important intellectual content: Dr. Haghikia, Dr. Hellwig, Dr. Wiendl, Dr. Ziegler, Dr. Gold. Administrative, technical, and material support: Dr. Stroet, Dr. Goelz.

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