Mode of action and clinical studies with fumarates in multiple sclerosis

Experimental Neurology

Volumn 262, Issue Part A, 2014, Pages 52-56

  Salmen, Anke ^a   Gold, Ralf ^a  

^a ST JOSEF HOSPITAL   (Germany)

Author keywords

Dimethyl fumarate; DMF; Immunomodulation; Neuroprotection; RRMS

Indexed keywords

FUMARIC ACID DIMETHYL ESTER; PLACEBO; FUMARIC ACID DERIVATIVE; IMMUNOLOGIC FACTOR; NEUROPROTECTIVE AGENT;

ABDOMINAL PAIN; BACKACHE; CELLULITIS; CLINICAL EFFECTIVENESS; CLINICAL STUDY; DEPRESSION; DISEASE ASSOCIATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG FATALITY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; GASTRITIS; GASTROENTERITIS; GASTROINTESTINAL SYMPTOM; HEADACHE; HISTORY; HOT FLUSH; HUMAN; IMMUNOMODULATION; INFECTION; MULTIPLE SCLEROSIS; MUSCLE STRAIN; NEUROPROTECTION; NONHUMAN; OVARY CYST; PNEUMONIA; PROTEINURIA; PRURITUS; QUALITY OF LIFE; RELAPSE; REVIEW; TREATMENT OUTCOME; TREATMENT PLANNING; CLINICAL TRIAL (TOPIC);

CLINICAL TRIALS AS TOPIC; FUMARATES; HUMANS; IMMUNOLOGIC FACTORS; MULTIPLE SCLEROSIS; NEUROPROTECTIVE AGENTS;

EID: 84908658236     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.02.015     Document Type: Review

References (50)

1. Albrecht P., Bouchachia I., Goebels N., Henke N., Hofstetter H.H., Issberner A., Kovacs Z., Lewerenz J., Lisak D., Maher P., Mausberg A.K., Quasthoff K., Zimmermann C., Hartung H.P., Methner A. Effects of dimethyl fumarate on neuroprotection and immunomodulation. J. Neuroinflammation 2012, 9:163.
2. Altmeyer P.J., Matthes U., Pawlak F., Hoffmann K., Frosch P.J., Ruppert P., Wassilew S.W., Horn T., Kreysel H.W., Lutz G., et al. Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J. Am. Acad. Dermatol. 1994, 30:977-981.
3. Bar-Or A., Gold R., Kappos L., Arnold D.L., Giovannoni G., Selmaj K., O'Gorman J., Stephan M., Dawson K.T. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the DEFINE study. J. Neurol. 2013, 260:2297-2305.
4. Burton J.M., O'Connor P.W., Hohol M., Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst. Rev. 2012, 12:CD006921.
5. Comi G., Filippi M., Barkhof F., Durelli L., Edan G., Fernandez O., Hartung H., Seeldrayers P., Sorensen P.S., Rovaris M., Martinelli V., Hommes O.R. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001, 357:1576-1582.
6. Comi G., Martinelli V., Rodegher M., Moiola L., Bajenaru O., Carra A., Elovaara I., Fazekas F., Hartung H.P., Hillert J., King J., Komoly S., Lubetzki C., Montalban X., Myhr K.M., Ravnborg M., Rieckmann P., Wynn D., Young C., Filippi M. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009, 374:1503-1511.
7. Ermis U., Weis J., Schulz J.B. PML in a patient treated with fumaric acid. N. Engl. J. Med. 2013, 368:1657-1658.
8. Evans C., Beland S.G., Kulaga S., Wolfson C., Kingwell E., Marriott J., Koch M., Makhani N., Morrow S., Fisk J., Dykeman J., Jette N., Pringsheim T., Marrie R.A. Incidence and prevalence of multiple sclerosis in the Americas: a systematic review. Neuroepidemiology 2013, 40:195-210.
9. Flensner G., Landtblom A.M., Soderhamn O., Ek A.C. Work capacity and health-related quality of life among individuals with multiple sclerosis reduced by fatigue: a cross-sectional study. BMC Public Health 2013, 13:224.
10. Fox R.J., Miller D.H., Phillips J.T., Hutchinson M., Havrdova E., Kita M., Yang M., Raghupathi K., Novas M., Sweetser M.T., Viglietta V., Dawson K.T. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N. Engl. J. Med. 2012, 367:1087-1097.
11. Gambichler T., Scola N., Rotterdam S., Hoxtermann S., Haghikia A., Faissner S., Kreuter A., Bechara F.G., Altmeyer P., Chan A. Monitoring peripheral blood CD4(+) intracellular adenosine triphosphate concentration in patients with psoriasis treated with fumaric acid esters. Acta Derm. Venereol. 2012, 92:364-366.
12. Gold R., Kappos L., Arnold D.L., Bar-Or A., Giovannoni G., Selmaj K., Tornatore C., Sweetser M.T., Yang M., Sheikh S.I., Dawson K.T. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med. 2012, 367:1098-1107.
13. Gold R., Linington C., Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006, 129:1953-1971.
14. Hafler D.A., Slavik J.M., Anderson D.E., O'Connor K.C., De Jager P., Baecher-Allan C. Multiple sclerosis. Immunol. Rev. 2005, 204:208-231.
15. Haghikia A., Perrech M., Pula B., Ruhrmann S., Potthoff A., Brockmeyer N.H., Goelz S., Wiendl H., Linda H., Ziemssen T., Baranzini S.E., Kall T.B., Bengel D., Olsson T., Gold R., Chan A. Functional energetics of CD4+-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders. PLoS One 2011, 6:e18506.
16. Hartung H.P., Gonsette R., Konig N., Kwiecinski H., Guseo A., Morrissey S.P., Krapf H., Zwingers T. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002, 360:2018-2025.
17. Hohlfeld R., Wekerle H. Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines. Proc. Natl. Acad. Sci. U. S. A. 2004, 101(Suppl. 2):14599-14606.
18. Hoxtermann S., Nuchel C., Altmeyer P. Fumaric acid esters suppress peripheral CD4- and CD8-positive lymphocytes in psoriasis. Dermatology 1998, 196:223-230.
19. Hutchinson M., Fox R.J., Miller D.H., Phillips J.T., Kita M., Havrdova E., O'Gorman J., Zhang R., Novas M., Viglietta V., Dawson K.T. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study. J. Neurol. 2013, 260:2286-2296.
20. Jacobs L.D., Beck R.W., Simon J.H., Kinkel R.P., Brownscheidle C.M., Murray T.J., Simonian N.A., Slasor P.J., Sandrock A.W. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N. Engl. J. Med. 2000, 343:898-904.
21. Kappos L., Gold R., Miller D.H., MacManus D.G., Havrdova E., Limmroth V., Polman C.H., Schmierer K., Yousry T.A., Eraksoy M., Meluzinova E., Dufek M., Yang M., Dawson K., O'Neill G.N. 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, 18:314-321.
22. Kappos L., Gold R., Miller D.H., Macmanus D.G., Havrdova E., Limmroth V., Polman C.H., Schmierer K., Yousry T.A., Yang M., Eraksoy M., Meluzinova E., Rektor I., Dawson K.T., Sandrock A.W., O'Neill G.N. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008, 372:1463-1472.
23. Kappos L., Polman C.H., Freedman M.S., Edan G., Hartung H.P., Miller D.H., Montalban X., Barkhof F., Bauer L., Jakobs P., Pohl C., Sandbrink R. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology 2006, 67:1242-1249.
24. Kingwell E., Marriott J.J., Jette N., Pringsheim T., Makhani N., Morrow S.A., Fisk J.D., Evans C., Beland S.G., Kulaga S., Dykeman J., Wolfson C., Koch M.W., Marrie R.A. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol. 2013, 13:128.
25. Koziolek M.J., Tampe D., Bahr M., Dihazi H., Jung K., Fitzner D., Klingel R., Muller G.A., Kitze B. Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis. J. Neuroinflammation 2012, 9:80.
26. Lin S.X., Lisi L., Dello Russo C., Polak P.E., Sharp A., Weinberg G., Kalinin S., Feinstein D.L. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro 2011, 3.
27. Linker R.A., Lee D.H., Ryan S., van Dam A.M., Conrad R., Bista P., Zeng W., Hronowsky X., Buko A., Chollate S., Ellrichmann G., Bruck W., Dawson K., Goelz S., Wiese S., Scannevin R.H., Lukashev M., Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011, 134:678-692.
28. Litjens N.H., Burggraaf J., van Strijen E., van Gulpen C., Mattie H., Schoemaker R.C., van Dissel J.T., Thio H.B., Nibbering P.H. Pharmacokinetics of oral fumarates in healthy subjects. Br. J. Clin. Pharmacol. 2004, 58:429-432.
29. Liu Y., Kern J.T., Walker J.R., Johnson J.A., Schultz P.G., Luesch H. A genomic screen for activators of the antioxidant response element. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:5205-5210.
30. Lublin F.D., Reingold S.C. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996, 46:907-911.
31. MacManus D.G., Miller D.H., Kappos L., Gold R., Havrdova E., Limmroth V., Polman C.H., Schmierer K., Yousry T.A., Eraksoy M., Meluzinova E., Dufek M., Yang M., O'Neill G.N., Dawson K. BG-12 reduces evolution of new enhancing lesions to T1-hypointense lesions in patients with multiple sclerosis. J. Neurol. 2011, 258:449-456.
32. Magana S.M., Keegan B.M., Weinshenker B.G., Erickson B.J., Pittock S.J., Lennon V.A., Rodriguez M., Thomsen K., Weigand S., Mandrekar J., Linbo L., Lucchinetti C.F. Beneficial plasma exchange response in central nervous system inflammatory demyelination. Arch. Neurol. 2011, 68:870-878.
33. Mrowietz U., Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity. Trends Mol. Med. 2005, 11:43-48.
34. 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, 141:424-429.
35. Nieboer C., de Hoop D., Langendijk P.N., van Loenen A.C., Gubbels J. Fumaric acid therapy in psoriasis: a double-blind comparison between fumaric acid compound therapy and monotherapy with dimethylfumaric acid ester. Dermatologica 1990, 181:33-37.
36. Ockenfels H.M., Schultewolter T., Ockenfels G., Funk R., Goos M. The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network. Br. J. Dermatol. 1998, 139:390-395.
37. Papadopoulou A., D'Souza M., Kappos L., Yaldizli O. Dimethyl fumarate for multiple sclerosis. Expert Opin. Investig. Drugs 2010, 19:1603-1612.
38. Scannevin R.H., Chollate S., Jung M.Y., Shackett M., Patel H., Bista P., Zeng W., Ryan S., Yamamoto M., Lukashev M., Rhodes K.J. 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, 341:274-284.
39. Schimrigk S., Brune N., Hellwig K., Lukas C., Bellenberg B., Rieks M., Hoffmann V., Pohlau D., Przuntek H. 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.
40. Schroder A., Linker R.A., Gold R. Plasmapheresis for neurological disorders. Expert. Rev. Neurother. 2009, 9:1331-1339.
41. Schweckendiek W. Treatment of psoriasis vulgaris. Med. Monatsschr. 1959, 13:103-104.
42. Stoof T.J., Flier J., Sampat S., Nieboer C., Tensen C.P., Boorsma D.M. The antipsoriatic drug dimethylfumarate strongly suppresses chemokine production in human keratinocytes and peripheral blood mononuclear cells. Br. J. Dermatol. 2001, 144:1114-1120.
43. Stroet A., Linker R.A., Gold R. Advancing therapeutic options in multiple sclerosis with neuroprotective properties. J. Neural Transm. 2013, 120(Suppl. 1):S49-S53.
44. Sweetser M.T., Dawson K.T., Bozic C. Manufacturer's response to case reports of PML. N. Engl. J. Med. 2013, 368:1659-1661.
45. Thompson A.J., Toosy A.T., Ciccarelli O. Pharmacological management of symptoms in multiple sclerosis: current approaches and future directions. Lancet Neurol. 2010, 9:1182-1199.
46. van Horssen J., Witte M.E., Schreibelt G., de Vries H.E. Radical changes in multiple sclerosis pathogenesis. Biochim. Biophys. Acta 2011, 1812:141-150.
47. van Oosten B.W., Killestein J., Barkhof F., Polman C.H., Wattjes M.P. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N. Engl. J. Med. 2013, 368:1658-1659.
48. Vandermeeren M., Janssens S., Borgers M., Geysen J. Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM-1 expression in human endothelial cells. Biochem. Biophys. Res. Commun. 1997, 234:19-23.
49. Wierinckx A., Breve J., Mercier D., Schultzberg M., Drukarch B., Van Dam A.M. Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J. Neuroimmunol. 2005, 166:132-143.
50. 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.