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BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis

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Abstract

BG-12, an immunomodulatory agent, reduces frequency of new gadolinium-enhancing (Gd+) lesions in relapsing multiple sclerosis (MS). This study reports the effect of 240 mg BG-12 orally three times daily (tid) for 24 weeks on the evolution of new Gd+ lesions to T1-hypointense lesions. Brain magnetic resonance imaging (MRI) scans from patients in placebo and 240 mg BG-12 tid arms of a phase 2b study were examined retrospectively. Included patients had at least one new Gd+ lesion from weeks 4 to 12. Week 24 scans were analyzed for number and proportion of new Gd+ lesions that evolved to T1-hypointense lesions. Eighteen patients receiving BG-12 and 38 patients receiving placebo were included in the analysis. The analysis tracked 147 new Gd+ lesions in patients from the BG-12 group and 221 Gd+ lesions in patients from the placebo group. The percentage of Gd+ lesions that evolved to T1-hypointense lesions was 34% lower with BG-12 treatment versus placebo (29%, BG-12; 44%, placebo; odds ratio 0.51; 95% confidence interval 0.43, 0.61; p < 0.0001). In addition to reducing frequency of new Gd+ lesions, BG-12 significantly reduced probability of their evolution to T1-hypointense lesions in patients with MS compared with placebo.

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Acknowledgments

The authors acknowledge the contributions of Hema Gowda and Matthew Hasson, Scientific Connexions, Newtown, PA, USA, for technical and editorial assistance in preparing this manuscript for submission. Their work was funded by Biogen Idec, Inc. The authors also acknowledge the role of Virginia Santana with respect to MRI data management. Ludwig Kappos is supported by the Swiss MS Society. Eva Havrdova is supported by the Czech Ministry of Education (Research Program MSM 0021620849). This study was supported by Biogen Idec. Funding was received from the UK Department of Health’s National Institute for Health Research Biomedical Research Center’s funding scheme (UCLH/UCL Comprehensive Biomedical Research Trust). The NMR Research Unit at the UCL Institute of Neurology is supported by the MS Society of Great Britain and Northern Ireland. Statistical analyses were conducted by M. Yang, MS, Biogen Idec, Cambridge, MA. Please see online resource 1 for a list of BG-12 Phase 2b Study Investigators.

Conflict of interest

D.G. MacManus declares no conflicts of interest. D.H. Miller has received honoraria through payments to his employer, UCL Institute of Neurology, for advisory committees and/or consultancy in multiple sclerosis studies from BayerSchering, Biogen Idec, GlaxoSmithKline, and Novartis. He has received research grant support through his employer for performing central MRI analysis for multiple sclerosis trials from Biogen Idec, GlaxoSmithKline, and Novartis. L. Kappos has served as a principal investigator and member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. Sponsoring companies for these trials include Acorda Therapeutics, Actelion Pharmaceuticals, Allozyne, BaroFold, Bayer Health Care, BayerSchering Pharma, Bayhill, Biogen Idec, Boehringer-Ingelheim, Eisai, Elan, Genmab, GlaxoSmithKline, Merck-Serono, MediciNova, Novartis, Sanofi-Aventis, Santhera Pharmaceuticals, Shire, Roche, Teva, UCB, Wyeth, and others. He has lectured at medical conferences or in public on various aspects of the diagnosis and management of multiple sclerosis; in many cases these lectures have been sponsored by nonrestricted educational grants from one or another of the above-listed companies. Honoraria and other payments for all these activities have been exclusively used for funding research of his department. Research and the clinical operations (nursing and patient care services) of the MS Center in Basel have been supported by nonrestricted grants from one or more of these companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, and the Gianni Rubatto, Novartis, and Roche Research Foundations. R. Gold has served as a speaker or consultant for and received scientific grant support from BayerSchering, Biogen Idec, Merck-Serono, Novartis, and Teva. E. Havrdova has received honoraria for lecturing and consulting from Bayer Health Care, Biogen Idec, Genzyme, Merck-Serono, Novartis, Sanofi-Aventis, and Teva. She has received funding for clinical trials and served on advisory boards for Actelion, Bayer Health Care, Biogen Idec, Genzyme, GlaxoSmithKline, Merck-Serono, Novartis, Sanofi-Aventis, and Teva. V. Limmroth has received research support and honoraria for consultancy from Antisense Therapeutics, Bayer, Biogen Idec, GlaxoSmithKline, Merck-Serono, MSD, Pfizer, Sanofi-Aventis, and Teva. C.H. Polman has received consulting fees from Actelion, Antisense Therapeutics, BayerSchering, Biogen Idec, GlaxoSmithKline, Merck-Serono, Novartis, Roche, Teva, and UCB; lecture fees from Biogen Idec, Novartis, Schering AG, and Teva; and grant support from BayerSchering, Biogen Idec, GlaxoSmithKline, Merck-Serono, Novartis, Teva, and UCB. K. Schmierer received research support from Biogen Idec to perform the MRI analysis of the phase 2b trial of BG-12. He has received honoraria for speaking from Merck-Serono, Novartis, and Sanofi-Aventis. T.A. Yousry has served on a scientific advisory board for UCB; received honoraria and funding for travel for serving on scientific boards for Biogen Idec; and received research support from Biogen Idec, GlaxoSmithKline, Novartis, the NIHR UCLH Comprehensive Biomedical Research Centre, the MS Society of Great Britain and Northern Ireland, the MRC, and the Wellcome Trust. He serves on the editorial board for European Radiology. M. Eraksoy serves on the medical advisory board for Biogen Idec. E. Meluzinova declares no conflicts of interest. M. Dufek has served as a subinvestigator for a clinical trial for Biogen Idec (109MS301). M. Yang, K. Dawson, and G.N. O’Neill are employees of and have equity interest in Biogen Idec.

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Authors and Affiliations

  1. NMR Research Unit, University College London Institute of Neurology, Queen Square, London, WCIN 3BG, UK

    D. G. MacManus, D. H. Miller, K. Schmierer & T. A. Yousry

  2. Centre for Neuroscience and Trauma (Neuroimmunology Group), Blizard Institute of Cell and Molecular Science, Barts and The London Queen Mary School of Medicine and Dentistry, London, E1 1BB, UK

    K. Schmierer

  3. Department of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    L. Kappos

  4. University Clinic Bochum at St. Josef Hospital, Gudrunstr. 56, 44791, Bochum, Germany

    R. Gold

  5. Charles University in Prague, First Faculty of Medicine, Kateřinská 32, 121 08, Prague 2, Czech Republic

    E. Havrdova

  6. Cologne City Hospitals, University of Cologne, Ostmerheimer Str. 200, 51109, Cologne, Germany

    V. Limmroth

  7. VU Medical Centre, P. O. Box 7057, 1007 MB, Amsterdam, The Netherlands

    C. H. Polman

  8. Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey

    M. Eraksoy

  9. Department of Neurology, 2nd Medical School of Charles University, Motol University Hospital, Prague, Czech Republic

    E. Meluzinova

  10. Masaryk University, Žerotínovo nám. 617/9, 60177, Brno, Czech Republic

    M. Dufek

  11. Biogen Idec, Inc, 14 Cambridge Center, Cambridge, MA, 02142, USA

    M. Yang, G. N. O’Neill & K. Dawson

Authors
  1. D. G. MacManus
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  2. D. H. Miller
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  3. L. Kappos
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  4. R. Gold
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  6. V. Limmroth
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  7. C. H. Polman
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  8. K. Schmierer
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  9. T. A. Yousry
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  11. E. Meluzinova
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  12. M. Dufek
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  13. M. Yang
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  14. G. N. O’Neill
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  15. K. Dawson
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Corresponding author

Correspondence to D. H. Miller.

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MacManus, D.G., Miller, D.H., Kappos, L. et al. BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis. J Neurol 258, 449–456 (2011). https://doi.org/10.1007/s00415-010-5777-z

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  • DOI: https://doi.org/10.1007/s00415-010-5777-z

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