Advances in the management of relapsing–remitting multiple sclerosis: role of oral dimethyl fumarate (BG-12)

References

• Peterson JW, Bö L, Mörk S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol. 2001;50:389–400.11558796
   PubMed Web of Science ®Google Scholar
• Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343(13):938–952.11006371
   PubMed Web of Science ®Google Scholar
• Li DK, Paty DW. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-beta1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferon-beta1a Subcutaneously in Multiple Sclerosis. Ann Neurol. 1999;46(2):197–206.10443885
   PubMed Web of Science ®Google Scholar
• Sormani MP, Bonzano L, Roccatagliata L, Cutter GR, Mancardi GL, Bruzzi P. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol. 2009;65(3):268–275.19334061
   PubMed Web of Science ®Google Scholar
• Loleit V, Biberacher V, Hemmer B. Current and future therapies targeting the immune system in multiple sclerosis. Curr Pharm Biotechnol. 2014;15:276–296.24938888
   PubMed Web of Science ®Google Scholar
• Trojano M, Lucchese G, Graziano G, et al Geographical variations in sex ratio trends over time in multiple sclerosis. PloS One. 2012;7(10):e48078.23133550
   PubMed Web of Science ®Google Scholar
• Salmen A, Gold R. Mode of action and clinical studies with fumarates in multiple sclerosis. Exp Neurol. 2014;262 Pt A:52–56.24568735
   PubMed Web of Science ®Google Scholar
• Wolfson C, Wolfson DB. The latent period of multiple sclerosis: a critical review. Epidemiology. 1993;4(5):464–470.8399696
   PubMed Web of Science ®Google Scholar
• Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: an umbrella review of systematic and meta-analyses. Lancet Neurol. 2015;14:263–273.25662901
   PubMed Web of Science ®Google Scholar
• Dörr J, Döring A, Paul F. Can we prevent or treat multiple sclerosis by individualised vitamin D supply? EPMA J. 2013;4(1):4.23356351
   PubMedGoogle Scholar
• International Multiple Sclerosis Genetics Consortium (IMSGC), Beecham AH, Patsopoulos NA, et al Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353–1360.24076602
   PubMed Web of Science ®Google Scholar
• Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain. 2003;126:770–782.12615637
   PubMed Web of Science ®Google Scholar
• Kurtzke JF, Beebe GW, Nagler B, Kurland LT, Auth TL. Studies on the natural history of multiple sclerosis–8. Early prognostic features of the later course of the illness. J Chronic Dis. 1977;30(12):819–830.591609
   PubMedGoogle Scholar
• Poser S, Poser W, Schlaf G, et al Prognostic indicators in multiple sclerosis. Acta Neurol Scand. 1986;74(5):387–392.3825497
   PubMed Web of Science ®Google Scholar
• Runmarker B, Andersen O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain. 1993; 116(Pt 1):117–134.8453453
   PubMed Web of Science ®Google Scholar
• Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 3. Multivariate analysis of predictive factors and models of outcome. Brain. 1991;114(Pt2):1045–1056.2043940
   PubMed Web of Science ®Google Scholar
• Leray E, Yaouang J, Le Page E, et al Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010;133:1900–1913.20423930
   PubMed Web of Science ®Google Scholar
• Veauthier C, Paul F. Sleep disorders in multiple sclerosis and their relationship to fatigue. Sleep Med. 2014;15:5–14.24360534
   PubMed Web of Science ®Google Scholar
• Hillman L. Caregiving in multiple sclerosis. Phys Med Rehabil Clin N Am. 2013;24(4):619–627.24314680
   PubMed Web of Science ®Google Scholar
• Ragonese P, Aridon P, Salemi G, D’Amelio M, Savettieri G. Mortality in multiple sclerosis: a review. Eur J Neurol. 2008;15:123–127.18217882
   PubMed Web of Science ®Google Scholar
• Goodin DS, Reder AT, Ebers GC, et al Survival in MS: a radomized cohort study 21 years after the start of the pivotal IFNβ-1b trial. Neurology. 2012;78(17):1315–1322.22496198
   PubMed Web of Science ®Google Scholar
• Ramagopalan S, Wasiak R, Cox AP. Using Twitter to investigate opinions about multiple sclerosis treatments: a descriptive, exploratory study. F1000Research. 2014;3:216.25520780
   PubMedGoogle Scholar
• Schweckendiek W. [Treatment of psoriasis vulgaris]. Med Monatsschr. 1959;13(2):103–104. German.13643669
   PubMedGoogle Scholar
• Mrowietz U, Christophers E, Altmeyer P. Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use. The German Fumaric Acid Ester Consensus Conference. Br J Dermatol. 1999;141(3):424–249.10584060
   PubMed Web of Science ®Google Scholar
• No authors listed. BG 12: BG 00012, BG 12/Oral Fumarate, FAG-201, second-generation fumarate derivative–Fumapharm/Biogen Idec. Drugs R D. 2005;6(4):229–230.15991882
   PubMedGoogle Scholar
• Kees F. Dimethyl fumarate: a Janus-faced substance? Expert Opin Pharmacother. 2013;14(11):1559–1567.23697607
   PubMed Web of Science ®Google Scholar
• Litjens NH, van Strijen E, van Gulpen C, et al In vitro pharmacokinetics of anti-psoriatic fumaric acid esters. BMC Pharmacol. 2004;4:22.15479475
   PubMedGoogle Scholar
• Rostami-Yazdi M, Clement B, Mrowietz U. Pharmacokinetics of anti-psoriatic fumaric acid esters in psoriasis patients. Arch Dermatol Res. 2010;302(7):531–538.20574745
   PubMed Web of Science ®Google Scholar
• Werdenberg D, Joshi R, Wolffram S, Merkle HP, Langguth P. Presystemic Metabolism and intestinal absorption of antipsoriatic fumaric acid esters. Biopharm Drug Dispos. 2003;24:259–273.12973823
   PubMed Web of Science ®Google Scholar
• Rostami-Yazdi M, Clement B, Schmidt TJ, Schinor D, Mrowietz U. Detection of metabolites of fumaric acid esters in human urine: implications for their mode of action. J Invest Dermatol. 2009;129:231–234.18704112
   PubMed Web of Science ®Google Scholar
• Zoghi S, Amirghofran Z, Nikseresht A, Ashjazadeh N, Kamali-Sarvestani E, Rezaei N. Cytokine secretion pattern in treatment of lymphocytes of multiple sclerosis patients with fumaric acid esters. Immunol Invest. 2011;40:581–596.21510778
   PubMed Web of Science ®Google Scholar
• Rubant SA, Ludwig RJ, Diehl S, et al Dimethylfumarate reduces leukocyte rolling in vivo through modulation of adhesion molecule expression. J Invest Dermatol. 2008;128:326–331.17671516
   PubMed Web of Science ®Google Scholar
• Vandermeeren M, Janssens S, Wouters H, et al Dimethylfumarate is an inhibitor of cytokine-induced nuclear translocation of NF-kappa B1, but not ReIA in normal human dermal fibroblast cells. J Invest Dermatol. 2001;116(1):124–130.11168807
   PubMed Web of Science ®Google Scholar
• Albrecht P, Bouchachia I, Goebels N, et al Effects of dimethyl fumarate on neuroprotection and immunomodulation. J Neuroinflammation. 2012;9:163.22769044
   PubMed Web of Science ®Google Scholar
• Wilms H, Sievers J, Rickert U, Rostami-Yazdi M, Mrowietz U, Lucius R. 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 Neuroinflammation. 2010;7:30.20482831
   PubMed Web of Science ®Google Scholar
• Zhu K, Mrowietz U. Inhibition of dendritic cell differentiation by fumaric acid esters. J Invest Dermatol. 2001;116(2):203–208.11179994
   PubMed Web of Science ®Google Scholar
• Treumer F, Zhu K, Gläser R, Mrowietz U. Dimethylfumarate is a potent inducer of apoptosis in human T cells. J Invest Dermatol. 2003;121(6): 1338–1388.
   Web of Science ®Google Scholar
• Schilling S, Goelz S, Linker R, Luehder F, Gold R. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophase infiltration. Clin Exp Immunol. 2006;145:101–107.16792679
   PubMed Web of Science ®Google Scholar
• Itoh K, Wakabayashi N, Katoh Y, et al Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13(1):76–86.9887101
   PubMed Web of Science ®Google Scholar
• 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):678–692.21354971
   PubMed Web of Science ®Google Scholar
• Foresti R, Bains SK, Pitchumony TS, et al Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells. Pharmacol Res. 2013;76:132–148.23942037
   PubMed Web of Science ®Google Scholar
• Scannevin RH, Chollate S, Jung MY, et al Fumarates promote cytoprotection of central nervious system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. J Pharmacol Exp Ther. 2012;341(1):274–284.22267202
   PubMed Web of Science ®Google Scholar
• 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;13:604–610.16796584
   PubMed Web of Science ®Google Scholar
• Kappos L, Gold R, Miller DH, et al Effect of BG-12 on contrast-enhanced lesions in patients with relapsing–remitting multiple sclerosis: subgroup analyses from the phase 2b study. Mult Scler. 2012;18(3):314–321.21878455
   PubMed Web of Science ®Google Scholar
• MacManus DG, Miller DH, Kappos L, et al BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis. J Neurol. 2011;258:449–456.20963434
   PubMed Web of Science ®Google Scholar
• Gold R, Kappos L, Arnold DL, et al Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–1107.22992073
   PubMed Web of Science ®Google Scholar
• Fox RJ, Miller DH, Phillips JT, et al Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012; 367(12):1087–1097.22992072
   PubMed Web of Science ®Google Scholar
• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11): 1444–1452.6685237
   PubMed Web of Science ®Google Scholar
• Polman CH, Reingold SC, Edan G, et al Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol. 2005;58(6):840–846.16283615
   PubMed Web of Science ®Google Scholar
• 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;261:1794–1802.24989666
   PubMed Web of Science ®Google Scholar
• Arnold DL, Gold R, Kappos L, et al Magnetization transfer ratio in the delayed-release dimethyl fumarate DEFINE study. J Neurol. 2014;261: 2429–2437.25270680
   PubMed Web of Science ®Google Scholar
• 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):1582–1594.24139424
   PubMed Web of Science ®Google Scholar
• Biogen Idec. Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate (DMF)-Treated Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) (ASSURE). Available from: https://clinicaltrials.gov/ct2/show/NCT02090413 NLM identifier: NCT02090413 Accessed April 18, 2015.
   Google Scholar
• Tornatore C, Amjad F. Attenuation of dimethyl fumarate-related gastrointestinal symptoms with montelukast (P7.251). Neurology. 2014;82(10 Suppl P7):251.
   Google Scholar
• US Food and Drug Administration. FDA Approved Labeling (Tecfidera, NDA 204063). Silver Spring: US Food and Drug Administration; 2013 Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf. Accessed February 26, 2015.
   Google Scholar
• Lu E, Wang BW, Alwan S, et al A Review of safety-related pregnancy data surrounding the oral disease-modifying drugs for multiple sclerosis. CNS Drugs. 2014;28:89–94.24343726
   PubMed Web of Science ®Google Scholar
• Burness CB, Deeks ED. Dimethyl fumarate: a review of its use in patients with relapsing-remitting multiple sclerosis. CNS Drugs. 2014;28(4):373–387.24623127
   PubMed Web of Science ®Google Scholar
• Center for Drug Evaluation and Research. Medical Review(s). Application Number: 204063Orig1s000. Silver Spring: US Food and Drug Administration; 2013 Available from: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204063Orig1s000MedR.pdf. Accessed February 26, 2015.
   Google Scholar
• Oh CJ, Kim JY, Choi YK, et al Dimethylfumarate Attenuates renal fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. PloS One. 2012;7(10):e45870.23056222
   PubMed Web of Science ®Google Scholar
• Munday R, Smith BL, Munday CM. Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats. Chem Biol Interact. 2005;155:140–147.16045903
   PubMed Web of Science ®Google Scholar
• Biogen Idec. Dimethyl Fumarate (DMF) Observational Study (ESTEEM). Available from: https://clinicaltrials.gov/ct2/show/NCT02047097?term=MS+and+ESTEEM&rank=1 NLM identifier: NCT02047097 Accessed February 26, 2015.
   Google Scholar
• Kothary N, Diak IL, Brinker A, Bezabeh S, Avigan M, Dal Pan G. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol. 2011;65(3):546–551.21514689
   PubMed Web of Science ®Google Scholar
• van Oosten BW, Killestein J, Barkhof F, Polman CH, Wattjes MP. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med. 2013;368(17):1658–1659.23614604
   PubMed Web of Science ®Google Scholar
• Ermis U, Weis J, Schulz J. PML in a patient treated with fumaric acid. N Engl J Med. 2013;368:1657–1658.23614603
   PubMed Web of Science ®Google Scholar
• Stoppe M, Thomä E, Liebert UG, et al Cerebellar manifestation of PML under fumarate and after efalizumab treatment of psoriasis. J Neurol. 2014;261:1021–1024.24638202
   PubMed Web of Science ®Google Scholar
• Buttmann M, Stoll G. Case reports of PML in patients treated for psoriasis. N Engl J Med. 2013;369(11):1081.
   Google Scholar
• Nieuwkamp DJ, Murk JL, van Oosten BW, et al PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. N Engl J Med. 2015;372(15):1474–1476.25853764
   PubMed Web of Science ®Google Scholar
• Sweetser MT, Dawson KT, Bozic C. Manufacturer’s response to case reports of PML. N Engl J Med. 2013;368(17):1659–1661.23614605
   PubMed Web of Science ®Google Scholar
• 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 (P3.179). Neurology. 2014;82(10 Suppl P3):179.
   Google Scholar
• US Food and Drug Administration. FDA Drug Safety Communication: FDA warns about case of rare brain infection PML with MS drug Tecfidera (dimethyl fumarate) Silver Spring: US Food and Drug Administration; 2014 Available from: http://www.fda.gov/Drugs/DrugSafety/ucm424625.htm. Accessed February 26, 2015.
   Google Scholar
• Rosenkranz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med. 2015;372(15): 1476–1478.25853765
   PubMed Web of Science ®Google Scholar
• Spencer CM, Crabtree-Hartman EC, Lehmann-Horn K, Cree BA, Zamvil SS. Reduction of CD8+ T lymphocytes in multiple sclerosis patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e76.25738172
   PubMed Web of Science ®Google Scholar
• 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):243–252.24150779
   PubMed Web of Science ®Google Scholar
• 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):253–257.24150778
   PubMed Web of Science ®Google Scholar
• 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):1958–1971.25315404
   PubMed Web of Science ®Google Scholar
• Heesen C, Cohen JA. Does the patient know best? Quality of Life assessment in multiple sclerosis trials. Mult Scler. 2014;20(2): 131–132.24493700
   PubMed Web of Science ®Google Scholar
• Fox RJ, Cree BA, De Sèze J, et al MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study. Neurology. 2014;82:1491–1498.24682966
   PubMed Web of Science ®Google Scholar
• Fine AJ, Sorbello A, Kortepeter C, Scarazzini L. Progressive multifocal leukoencephalopathy after natalizumab discontinuation. Ann Neurol. 2014;75:108–115.24242357
   PubMed Web of Science ®Google Scholar
• Jokubaitis VG, Li V, Kalincik T, et al Fingolimod after natalizumab and the risk of short-term relapse. Neurology. 2014;82:1204–1211.24610329
   PubMed Web of Science ®Google Scholar
• Rinaldi F, Seppi D, Calabrese M, Perini P, Gallo P. Switching therapy from natalizumab to fingolimod in relapsing-remitting multiple sclerosis: clinical and magnetic resonance imaging findings. Mult Scler. 2012;18(11):1640–1643.23100526
   PubMed Web of Science ®Google Scholar
• Giovannoni G, Naismith RT. Natalizumab to fingolimod washout in patients at risk of PML: when good intentions yield bad outcomes. Neurology. 2014;82:1196–1197.24610331
   PubMed Web of Science ®Google Scholar
• Vo KH, Barra M, Drago N, et al Clinical Management of Patients with Relapsing-Remitting Multiple Sclerosis Transitioning from Natalizumab to Dimethyl Fumarate. Presented at 2014 Joint Congress of European Neurology; May 31—June 3; Istanbul, Turkey.
   Google Scholar
• Hillman L, Gallaro D. Incidence of relapse during the first 6 months in a cohort of patients switched to dimethyl fumarate. 2014; Presented at: 2014 CMSC ACTRIMS Cooperative Meeting; May 28–31; 2014; Dallas, TX.
   Google Scholar
• Foley J, Hoyt T, Christensen A, Blatter A. A pilot study to assess disease state stability, efficacy, and tolerability in a natalizumab to dimethyl fumarate crossover design. Available from: http://onlinelibrary.ectrims-congress.eu/ectrims/2014/ACTRIMS-ECTRIMS2014/64578/john.foley.a.pilot.study.to.assess.disease.state.stability.efficacy.and.html Accessed February 26, 2014.
   Google Scholar
• Biogen Idec. Real-world Outcomes on Tecfidera® (BG00012, Dimethyl Fumarate) Post-Tysabri® (BG00002, Natalizumab) (STRATEGY). Available from: https://clinicaltrials.gov/ct2/show/NCT02159573 NLM identifier: NCT02159573 Accessed April 1, 2015.
   Google Scholar
• Mellen Center. Mellen Center Approaches: Use of DMF in MS. Cleveland: Cleveland Clinic Available from: http://my.clevelandclinic.org/ccf/media/files/Neurological-Institute/mellen-center/13-neu-718-dimethyl-fumarate-fact-sheet.pdf Accessed April 1, 2015.
   Google Scholar
• 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):57–66.24990854
   PubMed Web of Science ®Google Scholar
• Nicholas JA, Boster AL, Imitola J, O’Connell C, Racke MK. Design of oral agents for the management of multiple sclerosis: benefit and risk assessment for dimethyl fumarate. Drug Des Devel Ther. 2014;8: 897–908.
   Web of Science ®Google Scholar
• Bomprezzi R. Dimethyl fumarate in the treatment of relapsing-remitting multiple sclerosis: an overview. Ther Adv Neurol Disord. 2015;8(1): 20–30.25584071
   PubMed Web of Science ®Google Scholar
• Fox RJ. In the coming year we should abandon interferons and glatiramer acetate as first-line therapy for MS: yes. Mult Scler. 2013;19(1): 24–25.23303880
   PubMed Web of Science ®Google Scholar