Skip to main content

Dimethyl Fumarate: A Review in Relapsing-Remitting MS

Drugs volume 76, pages 243–254 (2016)Cite this article

Abstract

Dimethyl fumarate (Tecfidera®) is an oral disease-modifying agent indicated for the twice-daily treatment of relapsing forms of multiple sclerosis (MS) and relapsing-remitting MS (RRMS). It displays immunomodulating and neuroprotective properties, both of which may contribute to its efficacy in these settings. In two phase III trials of 2 years’ duration (DEFINE and CONFIRM), twice-daily dimethyl fumarate reduced clinical relapse (both the proportion of patients with MS relapse and the annualized relapse rate), as well as MRI measures of disease activity, versus placebo in adults with RRMS; the drug also reduced disability progression relative to placebo in one of the two studies (DEFINE). Dimethyl fumarate had an acceptable tolerability profile in these trials, with the most common tolerability issues being flushing and gastrointestinal events, which appear to be largely manageable. In the DEFINE and CONFIRM extension (ENDORSE), a minimum of 5 years of treatment with the drug was associated with continued benefit and no new/worsening tolerability signals. Although additional active comparator data are needed, dimethyl fumarate is an effective twice-daily treatment option for use in adults with RRMS, with the convenience of oral administration and an acceptable long-term tolerability profile.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. National Institute of Neurological Disorders and Stroke. Multiple sclerosis: hope through research. 2015. http://www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm. Accessed 3 Dec 2015.

  2. National Multiple Sclerosis Society. What is MS? 2015. http://www.nationalmssociety.org. Accessed 3 Dec 2015.

  3. Ortiz GG, Pacheco-Moises FP, Bitzer-Quintero OK, et al. Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Dev Immunol. 2013;2013:708659.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kim W, Zandona ME, Kim SH, et al. Oral disease-modifying therapies for multiple sclerosis. J Clin Neurol. 2015;11(1):9–19.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: when to start, when to change, when to stop? World J Clin Cases. 2015;3(7):545–55.

    PubMed  PubMed Central  Google Scholar 

  6. Biogen Inc. Tecfidera® (dimethyl fumarate) delayed-release capsules: US prescribing Information. 2014. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed 3 Dec 2015.

  7. Biogen Idec Ltd. Tecfidera gastro-resistant hard capsules: EU summary of product characteristics. 2015. http://www.ema.europa.eu/ema/. Accessed 3 Dec 2015.

  8. Burness CB, Deeks ED. Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs. 2014;28(4):373–87.

    CAS  Article  PubMed  Google Scholar 

  9. Scannevin RH, Chollate S, Jung MY, et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther. 2012;341(1):274–84.

    CAS  Article  PubMed  Google Scholar 

  10. Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain. 2011;134(Pt 3):678–92.

    Article  PubMed  Google Scholar 

  11. Wang Q, Chuikov S, Taitano S, et al. Dimethyl fumarate protects neural stem/progenitor cells and neurons from oxidative damage through Nrf2-ERK1/2 MAPK pathway. Int J Mol Sci. 2015;16(6):13885–907.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Lin SX, Lisi L, Russo CD, et al. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro. 2011;3(2).

  13. Albrecht P, Bouchachia I, Goebels N, et al. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflamm. 2012;9:163.

    CAS  Article  Google Scholar 

  14. Huang H, Taraboletti A, Shriver LP. Dimethyl fumarate modulates antioxidant and lipid metabolism in oligodendrocytes. Redox Biol. 2015;5:169–75.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Schulze-Topphoff U, Varrin-Doyer M, Pekarek K, et al. Dimethyl fumarate utilizes NRF2-independent and NRF2-dependent pathways for immune modulation [abstract no. S53.002]. Neurology. 2014;82(10 Suppl).

  16. Chen H, Assmann JC, Krenz A, et al. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. J Clin Invest. 2014;124(5):2188–92.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Parodi B, Rossi S, Morando S, et al. Fumarates modulate microglia activation through a novel HCAR2 signaling pathway and rescue synaptic dysregulation in inflamed CNS. Acta Neuropathol (Berl). 2015;130(2):279–95.

    CAS  Article  Google Scholar 

  18. Tang H, Lu JY, Zheng X, et al. The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem Biophys Res Commun. 2008;375(4):562–5.

    CAS  Article  PubMed  Google Scholar 

  19. Hanson J, Gille A, Zwykiel S, et al. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J Clin Invest. 2010;120(8):2910–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Wilms H, Sievers J, Rickert U, et al. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in vitro model of brain inflammation. J Neuroinflamm. 2010;7:30.

    Article  Google Scholar 

  21. Ghoreschi K, Bruck J, Kellerer C, et al. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J Exp Med. 2011;208(11):2291–303.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Peng H, Guerau-de-Arellano M, Mehta VB, et al. Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor kappaB (NF-kappaB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling. J Biol Chem. 2012;287(33):28017–26.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Schilling S, Goelz S, Linker R, et al. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clin Exp Immunol. 2006;145(1):101–7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Schimrigk S, Brune N, Hellwig K, et al. Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study. Eur J Neurol. 2006;13(6):604–10.

    CAS  Article  PubMed  Google Scholar 

  25. Peng H, Matos M, Wipke B, et al. Dimethyl fumarate alters microglia phenotype and protects neurons against proinflammatory toxic microenvironments [abstract no. P1.163]. Neurology. 2015;84(14 Suppl).

  26. Brenna M, Matos M, Sun C, et al. The NRF2 transcriptional target, OSGIN1, contributes to the cytoprotective properties of monomethyl fumarate [abstract no. P1.150]. Neurology. 2015;84(14 Suppl).

  27. Phillips JT, Fox RJ. BG-12 in multiple sclerosis. Semin Neurol. 2013;33(1):56–65.

    Article  PubMed  Google Scholar 

  28. Brennan M, Allaire N, Huss D, et al. Dimethyl fumarate and monomethyl fumarate are distinguished by non-overlapping pharmacodynamic effects in vivo [abstract no. P1.206]. Neurology. 2014;82(Suppl):10.

    Google Scholar 

  29. Brennan MS, Matos MF, Li B, et al. Dimethyl fumarate and monoethyl fumarate exhibit differential effects on KEAP1, NRF2 activation, and glutathione depletion in vitro. PLoS One. 2015;10(3):e0120254.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gillard GO, Collette B, Anderson J, et al. DMF, but not other fumarates, inhibits NF-kappaB activity in vitro in an Nrf2-independent manner. J Neuroimmunol. 2015;283:74–85.

    CAS  Article  PubMed  Google Scholar 

  31. Treumer F, Zhu K, Glaser R, et al. Dimethylfumarate is a potent inducer of apoptosis in human T cells. J Invest Dermatol. 2003;121(6):1383–8.

    CAS  Article  PubMed  Google Scholar 

  32. Vandermeeren M, Janssens S, Wouters H, et al. Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-kappa B1, but not RelA in normal human dermal fibroblast cells. J Invest Dermatol. 2001;116(1):124–30.

    CAS  Article  PubMed  Google Scholar 

  33. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. New Engl J Med. 2012;367(12):1098–107 (plus supplementary appendix).

    CAS  Article  PubMed  Google Scholar 

  34. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. New Engl J Med. 2012;367(12):1087–97 (plus supplementary appendix).

    CAS  Article  PubMed  Google Scholar 

  35. Woodworth J, Zhao Z, Stecher S. Oral BG-12 in combination with interferon beta-1a or glatiramer acetate: pharmacokinetics, safety and tolerability [abstract]. 28th Congress of ECTRIMS and 15th Annual Conference of RIMS; 2010.

  36. Sheikh SI, Nestorov I, Russell H, et al. Tolerability and pharmacokinetics of delayed-release dimethyl fumarate administered with and without aspirin in healthy volunteers. Clin Ther. 2013;35(10):1582–94.

    CAS  Article  PubMed  Google Scholar 

  37. Giovannoni G, Gold R, Fox RJ, et al. Delayed-release dimethyl fumarate and relapses requiring intravenous steroid use and MS-related hospitalizations: integrated analysis of the phase 3 DEFINE and CONFIRM studies [abstract no. PP1228]. J Neurol. 2014;261(Suppl 1):S303.

    Google Scholar 

  38. Gold R, Giovannoni G, Phillips JT, et al. Long-term efficacy of delayed-release dimethyl fumarate in newly diagnosed patients with RRMS: an integrated analysis of DEFINE, CONFIRM, and ENDORSE [abstract no. P7.227]. Neurology. 2015;84(14 Suppl).

  39. Bar-Or A, Gold R, Fox RJ, et al. Five-year follow-up of delayed-release dimethyl fumarate in RRMS: integrated clinical efficacy data from the DEFINE, CONFIRM, and ENDORSE studies [abstract no. P7.234]. Neurology. 2015;84(14 Suppl).

  40. Fernandez O, Giovannoni G, Fox RJ, et al. Efficacy of delayed-release dimethyl fumarate for RRMS in prior interferon users in the DEFINE and CONFIRM studies [abstract no. P7.231]. Neurology. 2015;84(14 Suppl).

  41. Phillips JT, Gold R, Giovannoni G, et al. Clinical efficacy of delayed-release dimethyl fumarate in newly diagnosed relapsing-remitting multiple sclerosis patients with highly active disease: an integrated analysis of the phase 3 DEFINE and CONFIRM studies [abstract no. P7.228]. Neurology. 2015;84(14 Suppl).

  42. Fernández Ó, Giovannoni G, Fox RJ, et al. Efficacy of delayed-release dimethyl fumarate for relapsing-remitting multiple sclerosis in prior interferon users with low clinical disease activity: integrated analysis of the phase 3 DEFINE and CONFIRM studies [abstract no. EP1318]. In: 31st Congress of ECTRIMS; 2015.

  43. Yousry T, Arnold DL, Fox RJ, et al. Five-year follow-up of delayed-release dimethyl fumarate in relapsing-remitting multiple sclerosis: MRI outcomes from DEFINE, CONFIRM, and ENDORSE [abstract no. P7.262]. Neurology. 2015;84(14 Suppl).

  44. Kappos L, Fox RJ, Gold R, et al. Delayed-release dimethyl fumarate and health-related quality of life (HRQoL) in relapsing-remitting multiple sclerosis (RRMS) patients according to prior therapy: integrated analysis of DEFINE and CONFIRM [abstract no. PP1238]. J Neurol. 2014;261(Suppl 1):S306.

    Google Scholar 

  45. Sarda SP, Kita M, Fox RJ, et al. An interim analysis of quality of life in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate [abstract no. P790]. Mult Scler. 2014;20(1 Suppl 1):413–4.

    Google Scholar 

  46. Kremenchutzky M, Fox RJ, Phillips JT, et al. Efficacy of delayed-release dimethyl fumarate vs glatiramer acetate on a novel composite outcome measure of inflammatory disease activity: post hoc analysis of the CONFIRM study [abstract no. P1063]. In: 31st Congress of ECTRIMS; 2015.

  47. Gold R, Giovannoni G, Phillips JT, et al. Efficacy of delayed-release dimethyl fumarate in early multiple sclerosis: post hoc analysis of the phase 3 DEFINE and CONFIRM studies according to baseline disability [abstract no. P565]. In: ECTRIMS; 2015.

  48. Miller D, Yousry T, Fox RJ, et al. Sustained low rate of brain volume loss with long-term delayed release dimethyl fumarate treatment in relapsing-remitting multiple sclerosis patients: results from the ENDORSE study [abstract no. P1072]. In: ECTRIMS; 2015.

  49. Fox RJ, Chan A, Gold R, et al. Characterization of absolute lymphocyte count profiles in MS patients treated with delayed-release dimethyl fumarate: considerations for patient management [abstract no. P606]. In: ECTRIMS; 2015.

  50. Miller DHF, Fox RJ, Phillips JT, et al. Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study. Neurology. 2015;84(11):1145–52.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. Arnold DL, Gold R, Kappos L, et al. Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study. J Neurol. 2014;261(9):1794–802.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  52. Viglietta V, Miller D, Bar-Or A, et al. Efficacy of delayed-release dimethyl fumarate in relapsing-remitting multiple sclerosis: integrated analysis of the phase 3 trials. Ann Clin Transl Neurol. 2015;2(2):103–18.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Kappos L, Giovannoni G, Gold R, et al. Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. Eur J Neurol. 2015;22(4):664–71.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. Bar-Or A, Gold R, Kappos L, et al. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study. J Neurol. 2013;260(9):2297–305.

    CAS  Article  PubMed  Google Scholar 

  55. Hutchinson M, Fox RJ, Miller DH, et al. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study. J Neurol. 2013;260(9):2286–96.

    CAS  Article  PubMed  Google Scholar 

  56. Gold R, Giovannoni G, Phillips JT, et al. Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS). Mult Scler. 2015;21(1):57–66.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. Arnold DL, Gold R, Kappos L, et al. Magnetization transfer ratio in the delayed-release dimethyl fumarate DEFINE study. J Neurol. 2014;261(12):2429–37.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. Kappos L, Gold R, Arnold DL, et al. Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: the DEFINE study. Mult Scler. 2014;20(2):243–52.

    Article  PubMed  Google Scholar 

  59. Kita M, Fox RJ, Phillips JT, et al. Effects of BG-12 (dimethyl fumarate) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: findings from the CONFIRM study. Mult Scler. 2014;20(2):253–7.

    CAS  Article  PubMed  Google Scholar 

  60. Kita M, Fox RJ, Gold R, et al. Effects of delayed-release dimethyl fumarate (DMF) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: an integrated analysis of the phase 3 DEFINE and CONFIRM studies. Clin Ther. 2014;36(12):1958–71.

    CAS  Article  PubMed  Google Scholar 

  61. Gold R, Phillips JT, Havradova E, et al. Delayed-release dimethyl fumarate and pregnancy: preclinical studies and pregnancy outcomes from clinical trial and postmarketing experience. Neurol Ther. 2015. doi:10.1007/s40120-015-0033-1.

    PubMed  PubMed Central  Google Scholar 

  62. Phillips JT, Selmaj K, Gold R, et al. Clinical significance of gastrointestinal and flushing events in patients with delayed-release dimethyl fumarate. Int J MS Care. 2015;17:236–43.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Phillips JT, Hutchinson M, Fox R, et al. Managing flushing and gastrointestinal events associated with delayed-release dimethyl fumarate: experiences of an international panel. Mult Scler Relat Disord. 2014 3(4):513–9.

    CAS  Article  PubMed  Google Scholar 

  64. Phillips JT, Erwin AA, Agrella S, et al. Consensus management of gastrointestinal events associated with delayed-release dimethyl fumarate: a Delphi study. Neurol Ther. 2015. doi:10.1007/s40120-015-0037-x.

    PubMed  PubMed Central  Google Scholar 

  65. Von Hehn C, Tornatore C, Li J, et al. Effect of bismuth subsalicylate on gastrointestinal events associated with delayed-release dimethyl fumarate: a double-blind, placebo-controlled study [abstract no. P052]. Mult Scler. 2014;20(1 Suppl 1):90.

    Google Scholar 

  66. Tornatore C, Amjad F. Attenuation of dimethyl fumarate-related gastrointestinal symptoms with montelukast [abstract P7.251 plus poster]. Neurology. 2014;82(10 Suppl).

  67. Sammarco C, Laing L, Herbert J. Strategies to reduce adverse events related to oral dimethyl fumarate [abstract no. P311 plus poster]. Mult Scler. 2014;20(1 Suppl 1):206.

    Google Scholar 

  68. Begus-Nahrmann Y, Niemczyk G, Schmid B, et al. Disparities and challenges to oral disease modifying MS therapies and the potential of individualised coaching [poster no. P1121]. In: 31st Congress of ECTRIMS; 2015.

  69. Fox EJ, Vasquez A, Grainger W, et al. Gastrointestinal tolerability of dimethyl fumarate in a multicenter, open-label study of patients with relapsing forms of multiple sclerosis (MANAGE). Int J MS Care. 2015. doi:10.7224/1537-2073.2014-101.

    Google Scholar 

  70. O’Gorman J, Russell HK, Li J, et al. Effect of aspirin pretreatment or slow dose titration on flushing and gastrointestinal events in healthy volunteers receiving delayed-release dimethyl fumarate. Clin Ther. 2015;37(7):1402–19.

    Article  PubMed  Google Scholar 

  71. Fox R, Gold R, Phillips JT, et al. Lymphocyte count reductions in relapsing-remitting multiple sclerosis (RRMS) patients treated with delayed-release dimethyl fumarate: an integrated analysis of the placebo-controlled studies [abstract]. Neurology. 2014;82(10 Suppl 1).

  72. European Medicines Agency. Updated recommendations to minimise the risk of the rare brain infection PML with Tecfidera [media release]. http://www.ema.europa.eu/. Accessed 23 Oct 2015.

  73. Lima MA. Progressive multifocal leukoencephalopathy: new concepts. Arq Neuropsiquiatr. 2013;71(9B):699–702.

    Article  PubMed  Google Scholar 

  74. McKee S. Biogen reports second case of PML [media release]. http://pharmatimes.com. Accessed 20 Jul 2015.

  75. Rosenkranz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med. 2015;372(15):1476–8.

    CAS  Article  PubMed  Google Scholar 

  76. Pozzilli C, Phillips JT, Fox R, et al. Long-term follow-up of the safety of delayed-release dimethyl fumarate in RRMS: interim results from the ENDORSE extension study [abstract no. P066 plus poster]. Neurology. 2015;84(14 Suppl):96–7.

    Google Scholar 

  77. Costello K, Halper J, Kalb R, et al. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. 2015. http://www.nationalmssociety.org. Accessed 3 Dec 2015.

  78. Canadian Agency for Drugs and Technology in Health. CADTH therapeutic review: recommendations for drug therapies for relapsing-remitting multiple sclerosis. 2013. https://www.cadth.ca/media/pdf/TR0004_RRMS_RecsReport_TR_e.pdf. Accessed 3 Dec 2015.

  79. Biogen. Gastrointestinal tolerability study of dimethyl fumarate (DMF) in participants with relapsing-remitting multiple sclerosis in Germany (TOLERATE). ClinicalTrials.gov identifier NCT02125604. 2015. https://www.clinicaltrials.gov. Accessed 3 Dec 2015.

  80. Tornatore C, Walsh J, Mann M, et al. Effect of montelukast on gastrointestinal tolerability in patients with relapsing forms of multiple sclerosis receiving delayed-release dimethyl fumarate: a multicenter, randomized, double-blind, placebo-controlled study (MITIGATE) [abstract no. P1.127]. Neurology. 2015;84(14 Suppl).

  81. Thomas RH, Wakefield RA. Oral disease-modifying therapies for relapsing-remitting multiple sclerosis. Am J Health-System Pharm. 2015;72(1):25–38.

    CAS  Article  Google Scholar 

  82. MS-UK Helpline. Oral MS medications ‘don’t improve treatment adherence’. 2015. http://www.ms-uk.org/drugsresearch. Accessed 24 Aug 2015.

  83. Scolding N, Barnes D, Cader S, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015;15(4):273–9.

    Article  PubMed  Google Scholar 

  84. Cohn S, Bermel R, Hara C, et al. Comparative tolerability and efficacy of dimethyl fumarate and fingolimod in multiple sclerosis [abstract no. P300]. Mult Scler. 2014;20(1 Suppl 1):201.

    Google Scholar 

  85. Nixon R, Bergvall N, Tomic D, et al. No evidence of disease activity: indirect comparisons of oral therapies for the treatment of relapsing-remitting multiple sclerosis. Adv Ther. 2014;31(11):1134–54.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  86. Hutchinson M, Fox RJ, Havrdova E, et al. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin. 2014;30(4):613–27.

    CAS  Article  PubMed  Google Scholar 

  87. National Institute for Health and Care Excellence. NICE technology appraisal guidance TA32, TA320, TA303 and TA254. 2002–2014. https://www.nice.org.uk. Accessed 3 Dec 2015.

  88. Zhang X, Hay JW, Niu X. Cost effectiveness of fingolimod, teriflunomide, dimethyl fumarate and intramuscular interferon-beta1a in relapsing-remitting multiple sclerosis. CNS Drugs. 2015;29(1):71–81.

    CAS  Article  PubMed  Google Scholar 

  89. Maruszczak MJ, Montgomery SM, Griffiths MJ, et al. Cost-utility of fingolimod compared with dimethyl fumarate in highly active relapsing-remitting multiple sclerosis (RRMS) in England. J Med Econ. 2015;18(11):874–85.

    Article  PubMed  Google Scholar 

  90. Iyer R, Sussman M, Fay M, et al. Association between time to treatment initiation of delayed-release dimethyl fumarate following MS diagnosis and medical costs in a real-world setting [poster no. P331]. In: 31st Congress of ECTRIMS; 2015.

  91. Cohan SL, LaGanke C, Tornatore C, et al. Real-world clinical outcomes in relapsing-remitting multiple sclerosis patients who switch from natalizumab to delayed-release dimethyl fumarate: preliminary analysis of a multicenter, retrospective, observational study (STRATEGY) [poster no. 3278]. Annual Meeting of the Consortum of Multiple Sclerosis Centers; 2015.

  92. Viglietta V, Vollmer T, Zhang R, et al. Safety and tolerability of delayed-release dimethyl fumarate administered as add on therapy to beta interferons or glatiramer acetate in relapsing-remitting multiple sclerosis (RRMS) patients [abstract]. Neurology. 2014;82(10 Suppl. 1).

Download references

Acknowledgments

During the peer review process, the manufacturer of dimethyl fumarate was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Emma D. Deeks

Authors
  1. Emma D. Deeks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emma D. Deeks.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: M. S. Freedman, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Canada; M. D. Kaufman, Knoxville Neurologic Clinic and University of Tennessee Medical Center, Knoxville, TN, USA.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Deeks, E.D. Dimethyl Fumarate: A Review in Relapsing-Remitting MS. Drugs 76, 243–254 (2016). https://doi.org/10.1007/s40265-015-0528-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0528-1

Keywords

  • Progressive Multifocal Leukoencephalopathy
  • Glatiramer Acetate
  • Fingolimod
  • Magnetization Transfer Ratio
  • Annualize Relapse Rate