Skip to main content
Erschienen in: Wiener klinische Wochenschrift 19-20/2019

07.10.2019 | original article

Dimethyl fumarate is efficacious in severe plaque psoriasis

Post hoc analysis from the BRIDGE trial in Austria

verfasst von: Paul Sator, Robert Loewe, Omid Zamani, Gregor Holzer, Peter Wolf, Alexander Mlynek, Thomas Berger, Leo Richter, Elisabeth Schuller

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 19-20/2019

Einloggen, um Zugang zu erhalten

Summary

Background

Fumaric acid esters are recommended in European guidelines for induction and maintenance treatment of patients with moderate to severe plaque psoriasis. A systemic medication with pure dimethyl fumarate without monoethyl fumarate salts was recently licensed in Europe.

Objective

The efficacy and safety of pure dimethyl fumarate were assessed in patients with severe (physician global assessment) plaque psoriasis in Austria in the BRIDGE trial.

Methods

In this double blind, randomized, placebo-controlled trial patients received 16-week treatment with pure dimethyl fumarate in a head to head comparison with dimethyl fumarate with monoethyl fumarate salts, which is licensed in Germany. In this post hoc analysis the efficacy and safety were assessed in patients with severe psoriasis in Austria.

Results

Efficacy measures significantly improved in both active treatment arms compared to placebo in 65 patients after 16 weeks of treatment. Physician global assessment of clear/almost clear in the dimethyl fumarate group was non-inferior to the dimethyl fumarate with monoethyl fumarate salts group 2 months after end of treatment. No serious adverse reaction occurred in patients with dimethyl fumarate in contrast to the second active treatment. Efficacy outcome was paralleled by quality of life improvements.

Conclusion

This is the first report of dimethyl fumarate in a severely affected population with plaque psoriasis. Dimethyl fumarate is effective and safe in the systemic treatment of adults with severe psoriasis (physician global assessment).
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Michalek IM, Loring B, John SM. A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol. 2017;31(2):205–12.PubMedCrossRef Michalek IM, Loring B, John SM. A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatol Venereol. 2017;31(2):205–12.PubMedCrossRef
2.
Zurück zum Zitat Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris—Update 2015—Short version—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015;29(12):2277–94.PubMedCrossRef Nast A, Gisondi P, Ormerod AD, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris—Update 2015—Short version—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2015;29(12):2277–94.PubMedCrossRef
3.
Zurück zum Zitat Nast A, Spuls PI, van der Kraaij G, et al. European S3-Guideline on the systemic treatment of psoriasis vulgaris—Update Apremilast and Secukinumab—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2017;31(12):1951–63.PubMedCrossRef Nast A, Spuls PI, van der Kraaij G, et al. European S3-Guideline on the systemic treatment of psoriasis vulgaris—Update Apremilast and Secukinumab—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol. 2017;31(12):1951–63.PubMedCrossRef
4.
Zurück zum Zitat Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303(1):1–10.PubMedCrossRef Mrowietz U, Kragballe K, Reich K, et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res. 2011;303(1):1–10.PubMedCrossRef
5.
Zurück zum Zitat Veilleux MS, Shear NH. Biologics in patients with skin diseases. J Allergy Clin Immunol. 2017;139(5):1423–30.PubMedCrossRef Veilleux MS, Shear NH. Biologics in patients with skin diseases. J Allergy Clin Immunol. 2017;139(5):1423–30.PubMedCrossRef
7.
Zurück zum Zitat Ronholt K, Iversen L. Old and new biological therapies for psoriasis. Int J Mol Sci. 2017;18(11):E2297.PubMedCrossRef Ronholt K, Iversen L. Old and new biological therapies for psoriasis. Int J Mol Sci. 2017;18(11):E2297.PubMedCrossRef
8.
Zurück zum Zitat Puig L, Carrascosa JM, Daudén E, et al. Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents. Actas Dermosifiliogr. 2009;100(5):386–413.PubMedCrossRef Puig L, Carrascosa JM, Daudén E, et al. Spanish evidence-based guidelines on the treatment of moderate-to-severe psoriasis with biologic agents. Actas Dermosifiliogr. 2009;100(5):386–413.PubMedCrossRef
9.
Zurück zum Zitat Papp KA, Tyring S, Lahfa M, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152(6):1304–12.PubMedCrossRef Papp KA, Tyring S, Lahfa M, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152(6):1304–12.PubMedCrossRef
10.
Zurück zum Zitat Ovejero-Benito MC, Munoz-Aceituno E, Reolid A, Saiz-Rodriguez M, Abad-Santos F, Dauden E. Pharmacogenetics and pharmacogenomics in moderate-to-severe psoriasis. Am J Clin Dermatol. 2018;19(2):209–22.PubMedCrossRef Ovejero-Benito MC, Munoz-Aceituno E, Reolid A, Saiz-Rodriguez M, Abad-Santos F, Dauden E. Pharmacogenetics and pharmacogenomics in moderate-to-severe psoriasis. Am J Clin Dermatol. 2018;19(2):209–22.PubMedCrossRef
11.
Zurück zum Zitat Mrowietz U, Christophers E, Altmeyer P. Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study. Br J Dermatol. 1998;138(3):456–60.PubMedCrossRef Mrowietz U, Christophers E, Altmeyer P. Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study. Br J Dermatol. 1998;138(3):456–60.PubMedCrossRef
12.
Zurück zum Zitat Carboni I, De Felice C, De Simoni I, Soda R, Chimenti S. Fumaric acid esters in the treatment of psoriasis: an Italian experience. J Dermatolog Treat. 2004;15(1):23–6.PubMedCrossRef Carboni I, De Felice C, De Simoni I, Soda R, Chimenti S. Fumaric acid esters in the treatment of psoriasis: an Italian experience. J Dermatolog Treat. 2004;15(1):23–6.PubMedCrossRef
13.
14.
Zurück zum Zitat Mrowietz U, Altmeyer P, Bieber T, Rocken M, Schopf RE, Sterry W. Treatment of psoriasis with fumaric acid esters (Fumaderm). J Dtsch Dermatol Ges. 2007;5(8):716–7.PubMedCrossRef Mrowietz U, Altmeyer P, Bieber T, Rocken M, Schopf RE, Sterry W. Treatment of psoriasis with fumaric acid esters (Fumaderm). J Dtsch Dermatol Ges. 2007;5(8):716–7.PubMedCrossRef
15.
Zurück zum Zitat 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
17.
Zurück zum Zitat Eminel S, Jin N, Rostami M, Dibbert S, Mrowietz U, Suhrkamp I. Dimethyl- and monomethylfumarate regulate indoleamine 2,3-dioxygenase (IDO) activity in human immune cells. Exp Dermatol. 2017;26(8):685–90.PubMedCrossRef Eminel S, Jin N, Rostami M, Dibbert S, Mrowietz U, Suhrkamp I. Dimethyl- and monomethylfumarate regulate indoleamine 2,3-dioxygenase (IDO) activity in human immune cells. Exp Dermatol. 2017;26(8):685–90.PubMedCrossRef
18.
Zurück zum Zitat Tahvili S, Zandieh B, Amirghofran Z. The effect of dimethyl fumarate on gene expression and the level of cytokines related to different T helper cell subsets in peripheral blood mononuclear cells of patients with psoriasis. Int J Dermatol. 2015;54(7):e254–e60.PubMedCrossRef Tahvili S, Zandieh B, Amirghofran Z. The effect of dimethyl fumarate on gene expression and the level of cytokines related to different T helper cell subsets in peripheral blood mononuclear cells of patients with psoriasis. Int J Dermatol. 2015;54(7):e254–e60.PubMedCrossRef
20.
Zurück zum Zitat Fiedler SE, Kerns AR, Tsang C, Tsang V, Bourdette D, Salinthone S. Dimethyl fumarate activates the prostaglandin EP2 receptor and stimulates cAMP signaling in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2016;475(1):19–24.PubMedCrossRef Fiedler SE, Kerns AR, Tsang C, Tsang V, Bourdette D, Salinthone S. Dimethyl fumarate activates the prostaglandin EP2 receptor and stimulates cAMP signaling in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2016;475(1):19–24.PubMedCrossRef
21.
Zurück zum Zitat Mrowietz U, Szepietowski JC, Loewe R, et al. Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm(R)—and placebo-controlled trial (BRIDGE). Br J Dermatol. 2017;176(3):615–23.PubMedCrossRef Mrowietz U, Szepietowski JC, Loewe R, et al. Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm(R)—and placebo-controlled trial (BRIDGE). Br J Dermatol. 2017;176(3):615–23.PubMedCrossRef
22.
Zurück zum Zitat Heelan K, Markham T. Fumaric acid esters as a suitable first-line treatment for severe psoriasis: an Irish experience. Clin Exp Dermatol. 2012;37(7):793–5.PubMedCrossRef Heelan K, Markham T. Fumaric acid esters as a suitable first-line treatment for severe psoriasis: an Irish experience. Clin Exp Dermatol. 2012;37(7):793–5.PubMedCrossRef
23.
Zurück zum Zitat Nieboer C, de Hoop D, Langendijk PN, van Loenen AC, 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(1):33–7.PubMedCrossRef Nieboer C, de Hoop D, Langendijk PN, van Loenen AC, 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(1):33–7.PubMedCrossRef
24.
Zurück zum Zitat 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(6):259–73.PubMedCrossRef 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(6):259–73.PubMedCrossRef
25.
Zurück zum Zitat Smith D. Fumaric acid esters for psoriasis: a systematic review. Ir J Med Sci. 2017;186(1):161–77.PubMedCrossRef Smith D. Fumaric acid esters for psoriasis: a systematic review. Ir J Med Sci. 2017;186(1):161–77.PubMedCrossRef
26.
Zurück zum Zitat Balak DM, Fallah Arani S, Hajdarbegovic E, et al. Efficacy, effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies. Br J Dermatol. 2016;175(2):250–62.PubMedCrossRef Balak DM, Fallah Arani S, Hajdarbegovic E, et al. Efficacy, effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies. Br J Dermatol. 2016;175(2):250–62.PubMedCrossRef
27.
Zurück zum Zitat Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, Luger T. Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis—a retrospective study (FUTURE). J Dtsch Dermatol Ges. 2009;7(7):603–11.PubMed Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, Luger T. Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis—a retrospective study (FUTURE). J Dtsch Dermatol Ges. 2009;7(7):603–11.PubMed
28.
Zurück zum Zitat Atwan A, Ingram JR, Abbott R, et al. Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2016;175(5):873–81.PubMedPubMedCentralCrossRef Atwan A, Ingram JR, Abbott R, et al. Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2016;175(5):873–81.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat O’Gorman J, Russell HK, Li J, Phillips G, Kurukulasuriya NC, Viglietta V. 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):1402–1419.e5.PubMedCrossRef O’Gorman J, Russell HK, Li J, Phillips G, Kurukulasuriya NC, Viglietta V. 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):1402–1419.e5.PubMedCrossRef
30.
Zurück zum Zitat Nast A, Boehncke WH, Mrowietz U, et al. German S3-guidelines on the treatment of psoriasis vulgaris (short version). Arch Dermatol Res. 2012;304(2):87–113.PubMedCrossRef Nast A, Boehncke WH, Mrowietz U, et al. German S3-guidelines on the treatment of psoriasis vulgaris (short version). Arch Dermatol Res. 2012;304(2):87–113.PubMedCrossRef
31.
Zurück zum Zitat Phillips TJ, Erwin AA, Agrella S, et al. Consensus management of gastrointestinal events associated with delayed-release dimethyl fumarate: a delphi study. Neurol Ther. 2015;4(2):137–46.CrossRef Phillips TJ, Erwin AA, Agrella S, et al. Consensus management of gastrointestinal events associated with delayed-release dimethyl fumarate: a delphi study. Neurol Ther. 2015;4(2):137–46.CrossRef
32.
Zurück zum Zitat Augustin M, Langenbruch A, Gutknecht M, et al. Definition of psoriasis severity in routine clinical care: current guidelines fail to capture the complexity of long-term psoriasis management. Br J Dermatol. 2018;179(6):1385–91.PubMedCrossRef Augustin M, Langenbruch A, Gutknecht M, et al. Definition of psoriasis severity in routine clinical care: current guidelines fail to capture the complexity of long-term psoriasis management. Br J Dermatol. 2018;179(6):1385–91.PubMedCrossRef
33.
Zurück zum Zitat Weger W, Heschl B, Salmhofer W, et al. Methotrexate vs. fumaric acid esters in moderate-to-severe chronic plaque psoriasis: data registry report on the efficacy under daily life conditions. J Eur Acad Dermatol Venereol. 2013;27(7):861–6.PubMedCrossRef Weger W, Heschl B, Salmhofer W, et al. Methotrexate vs. fumaric acid esters in moderate-to-severe chronic plaque psoriasis: data registry report on the efficacy under daily life conditions. J Eur Acad Dermatol Venereol. 2013;27(7):861–6.PubMedCrossRef
Metadaten
Titel
Dimethyl fumarate is efficacious in severe plaque psoriasis
Post hoc analysis from the BRIDGE trial in Austria
verfasst von
Paul Sator
Robert Loewe
Omid Zamani
Gregor Holzer
Peter Wolf
Alexander Mlynek
Thomas Berger
Leo Richter
Elisabeth Schuller
Publikationsdatum
07.10.2019
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 19-20/2019
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-019-01551-6

Weitere Artikel der Ausgabe 19-20/2019

Wiener klinische Wochenschrift 19-20/2019 Zur Ausgabe

mitteilungen der gesellschaft der ärzte in wien

Veranstaltungstipps