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Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing–remitting multiple sclerosis: subgroup analyses of the CONFIRM study

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Abstract

In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing–remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34 % [rate ratio 0.664 (95 % confidence interval 0.422–1.043)] to 53 % [0.466 (0.313–0.694)] and from 13 % [0.870 (0.551–1.373)] to 67 % [0.334 (0.226–0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing–remitting multiple sclerosis with varied demographic and disease characteristics.

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Acknowledgments

This study was supported by Biogen Idec Inc. (Weston, MA, USA). EH was supported by the Czech Ministry of Education, VZ MSM 0021620849 and PRVOUK-P26/LF1/4. The authors would like to thank the CONFIRM study investigators. Medical writing support and editorial assistance were provided by Samantha Holmes (CircleScience, Tytherington, UK), funded by Biogen Idec Inc.

Conflict of interest

Michael Hutchinson serves on a medical advisory board [BG00012] for Biogen Idec, is an assistant editor of Multiple Sclerosis Journal, and reports having received speaker’s honoraria from Bayer Schering, Biogen Idec, and Novartis, and research support from Dystonia Ireland and the Health Research Board of Ireland. Robert J. Fox reports having received consultant fees from Allozyne, Avanir, Biogen Idec, Novartis, Questcor, and Teva, and grant and research support from Novartis. David H. Miller reports having received honoraria from Bayer Schering Pharma, Biogen Idec, and GlaxoSmithKline and research grants from Apitope, Biogen Idec, GlaxoSmithKline, Novartis, Richmond Pharma, and Schering AG. J. Theodore Phillips reports having received honoraria from Acorda, Biogen Idec, Genzyme, Novartis, and Teva, and research support from Biogen Idec and Roche. Mariko Kita reports having received research support from Biogen Idec. Eva Havrdova reports having received honoraria from Bayer, Biogen Idec, Genzyme, Novartis, Serono, and Teva. John O’Gorman, Ray Zhang, Mark Novas, Vissia Viglietta, and Katherine T. Dawson are employees of Biogen Idec.

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Authors and Affiliations

  1. St. Vincent’s University Hospital, Elm Park, Donnybrook, Dublin 4, Ireland

    Michael Hutchinson

  2. The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, USA

    Robert J. Fox

  3. NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, UK

    David H. Miller

  4. Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA

    J. Theodore Phillips

  5. Virginia Mason Medical Center, Seattle, WA, USA

    Mariko Kita

  6. Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    Eva Havrdova

  7. Biogen Idec Inc., Weston, MA, USA

    John O’Gorman, Ray Zhang, Mark Novas, Vissia Viglietta & Katherine T. Dawson

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  1. Michael Hutchinson
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Correspondence to Michael Hutchinson.

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For the CONFIRM study investigators.

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Hutchinson, M., Fox, R.J., Miller, D.H. et al. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing–remitting multiple sclerosis: subgroup analyses of the CONFIRM study. J Neurol 260, 2286–2296 (2013). https://doi.org/10.1007/s00415-013-6968-1

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