Journal of Neurology

, Volume 260, Issue 9, pp 2297–2305 | Cite as

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

  • Amit Bar-OrEmail author
  • Ralf Gold
  • Ludwig Kappos
  • Douglas L. Arnold
  • Gavin Giovannoni
  • Krzysztof Selmaj
  • John O’Gorman
  • Monica Stephan
  • Katherine T. Dawson
Original Communication


In the double-blind, placebo-controlled, Phase 3 DEFINE study in patients with relapsing–remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) significantly reduced the proportion of patients relapsed (primary endpoint), the annualized relapse rate (ARR), and confirmed disability progression (secondary endpoints) at two years compared with placebo. We investigated the 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. The clinical efficacy of BG-12 was generally consistent across patient subgroups and reflected positive findings in the overall DEFINE study population. Treatment with BG-12 BID and TID reduced the proportion of patients relapsed and the ARR at two years compared with placebo in all patient subgroups. Reductions in the risk of relapse with BG-12 BID vs. placebo ranged from 68 % [hazard ratio 0.32 (95 % confidence interval (CI) 0.16–0.62)] to 26 % [0.74 (0.51–1.09)] and from 66 % [0.34 (0.23–0.50)] to 25 % [0.75 (0.42–1.36)] with BG-12 TID vs. placebo. BG-12 also reduced the risk of disability progression at two years compared with placebo in most subgroups of patients treated with the BID dosing regimen and in all subgroups treated with the TID regimen. These analyses indicate that treatment with BG-12 is consistently effective across a wide spectrum of patients with relapsing–remitting multiple sclerosis with varied demographic and disease characteristics.


BG-12 Dimethyl fumarate Multiple sclerosis Randomized controlled trial Subgroup analysis 



This study was supported by Biogen Idec Inc. (Weston, MA, USA). The authors would like to thank the DEFINE study investigators. Medical writing support and editorial assistance were provided by Samantha Holmes (CircleScience, Tytherington, UK), funded by Biogen Idec Inc.

Conflicts of interest

Amit Bar-Or reports having received honoraria and/or research support from Amplimmune, Aventis, Bayhill Therapeutics, Berlex, Biogen Idec, Diogenix, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Medimmune, Novartis, Ono Pharma, Receptos, Roche, Sanofi-Genzyme, and Teva Neuroscience. Ralf Gold reports having received honoraria from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience and research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Ludwig Kappos reports having received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim, Eisai, Elan, Genmab, GlaxoSmithKline, Glenmark, MediciNova, Merck Serono, Novartis, Roche, Sanofi-Aventis, Santhera, Shire, Teva Neuroscience, UCB, Wyeth, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, and Novartis and Roche Research Foundations. Douglas L. Arnold reports having received honoraria from Bayer HealthCare, Biogen Idec, Coronado Biosciences, Eli Lilly, EMD Serono, Genentech, Genzyme, NeuroRx Research, Novartis, Roche, and Teva and research support from Bayer HealthCare and Biogen Idec. Gavin Giovannoni reports having received research support from Bayer Schering, Biogen Idec, GW Pharma, Merck Serono, Merz, Novartis, Sanofi-Aventis, and Teva and honoraria from Bayer Schering, Biogen Idec, Eisai, Elan, Fiveprime, Genentech, Genzyme, GlaxoSmithKline, GW Pharma, Ironwood, Merck Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva, UCB Pharma, and Vertex Pharmaceuticals. Krzysztof Selmaj reports having received honoraria from Biogen Idec, Genzyme, Novartis, Ono, Roche, Synthon, and Teva. John O’Gorman, Monica Stephan, and Katherine T. Dawson are employees of Biogen Idec.

Supplementary material

415_2013_6954_MOESM1_ESM.pdf (427 kb)
Supplementary material 1 (PDF 426 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Amit Bar-Or
    • 1
    Email author
  • Ralf Gold
    • 2
  • Ludwig Kappos
    • 3
  • Douglas L. Arnold
    • 1
    • 4
  • Gavin Giovannoni
    • 5
  • Krzysztof Selmaj
    • 6
  • John O’Gorman
    • 7
  • Monica Stephan
    • 7
  • Katherine T. Dawson
    • 7
  1. 1.Montreal Neurological Institute and HospitalMcGill UniversityMontrealCanada
  2. 2.St. Josef HospitalRuhr UniversityBochumGermany
  3. 3.University Hospital Basel, NeurologyBaselSwitzerland
  4. 4.NeuroRx ResearchMontrealCanada
  5. 5.Blizard Institute, Barts and the London School of Medicine and DentistryQueen Mary University of LondonLondonUK
  6. 6.Medical University of LodzLodzPoland
  7. 7.Biogen Idec Inc.WestonUSA

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