Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study

Abstract Background: Mixtures of fumaric acid esters (FAE) are used as an oral systemic treatment for moderate to severe psoriasis. Large clinical studies with dimethylfumarate (DMF) monotherapy are scarce. Objectives: The objective of this study is to assess the effectiveness and long-term safety of high-dose DMF monotherapy in moderate to severe psoriasis. Methods: A prospective single-blinded follow-up study was performed in a cohort of patients treated with DMF. Patients were followed-up at fixed intervals. Assessment of consecutive photographs was performed by two observers. Primary outcome was a change in static physician global assessment (PGA) score. Safety outcome was defined as incidences of (serious) adverse events. Results: A total of 176 patients with moderate to severe psoriasis were treated with DMF for a median duration of 28 months. The median daily maintenance dosage of 480 mg was reached after a median of 8 months. Psoriasis activity decreased significantly by 1.7 out of five points. A total of 152 patients reported one or more adverse events, such as gastrointestinal complaints and flushing. Conclusions: High-dose DMF monotherapy is an effective and safe treatment option in moderate to severe psoriasis. It can be suggested that 50% of all patients may benefit from high-dose DMF monotherapy.

[1]  J. Weis,et al.  PML in a patient treated with fumaric acid. , 2013, The New England journal of medicine.

[2]  F. Barkhof,et al.  PML in a patient treated with dimethyl fumarate from a compounding pharmacy. , 2013, The New England journal of medicine.

[3]  A. Kimball,et al.  Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis. , 2012, Journal of the American Academy of Dermatology.

[4]  R. Dawe,et al.  Proteinuria with fumaric acid ester treatment for psoriasis , 2011, Clincal and Experimental Dermatology.

[5]  H. Thio,et al.  Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial , 2011, The British journal of dermatology.

[6]  S. Langham,et al.  Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review , 2011, BMC medical research methodology.

[7]  J. Barker,et al.  Treatment of severe, recalcitrant, chronic plaque psoriasis with fumaric acid esters: a prospective study , 2010, The British journal of dermatology.

[8]  G. Trevisan,et al.  Fumaric acid and its derivatives in the treatment of psoriasis vulgaris: our experience in forty-one patients. , 2009, Acta dermatovenerologica Croatica : ADC.

[9]  L. Naldi,et al.  European S3‐Guidelines on the systemic treatment of psoriasis vulgaris , 2009, Journal of the European Academy of Dermatology and Venereology : JEADV.

[10]  T. Luger,et al.  Efficacy and safety of fumaric acid esters in the long‐term treatment of psoriasis – A retrospective study (FUTURE) , 2009, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[11]  K. Reich,et al.  [15 years of fumaderm: fumaric acid esters for the systemic treatment of moderately severe and severe psoriasis vulgaris]. , 2009, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[12]  A. Dupuy,et al.  Global assessment of psoriasis severity and change from photographs: a valid and consistent method. , 2008, The Journal of investigative dermatology.

[13]  Wolf-Henning Boehncke,et al.  Dimethylfumarate reduces leukocyte rolling in vivo through modulation of adhesion molecule expression. , 2008, The Journal of investigative dermatology.

[14]  K. Wittkowski,et al.  Analytical approaches to reporting long-term clinical trial data. , 2008, Current medical research and opinion.

[15]  K. Asadullah,et al.  Dimethylfumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1. , 2007, The Journal of investigative dermatology.

[16]  P. Nibbering,et al.  Effects of monomethylfumarate on dendritic cell differentiation , 2006, The British journal of dermatology.

[17]  C. Griffiths,et al.  Fumaric acid esters for severe psoriasis: a retrospective review of 58 cases , 2005, The British journal of dermatology.

[18]  Khusru Asadullah,et al.  Dimethylfumarate for psoriasis: more than a dietary curiosity. , 2005, Trends in molecular medicine.

[19]  P. Nibbering,et al.  Pharmacokinetics of oral fumarates in healthy subjects. , 2004, British journal of clinical pharmacology.

[20]  Felix Treumer,et al.  Dimethylfumarate is a potent inducer of apoptosis in human T cells. , 2003, The Journal of investigative dermatology.

[21]  R. Willemze,et al.  Long‐term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis , 2003, The British journal of dermatology.

[22]  P. Nibbering,et al.  Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines , 2003, The British journal of dermatology.

[23]  U. Mrowietz,et al.  Inhibition of dendritic cell differentiation by fumaric acid esters. , 2001, The Journal of investigative dermatology.

[24]  J. Warzecha,et al.  [Multiple pathological fractures within the scope of DeToni-Debre-Fanconi syndrome after fumarate therapy in psoriasis]. , 2001, Der Unfallchirurg.

[25]  P. Altmeyer,et al.  Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use , 1999, The British journal of dermatology.

[26]  Ockenfels,et al.  The antipsoriatic agent dimethylfumarate immunomodulates T‐cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network , 1998, The British journal of dermatology.

[27]  T. Ottenhoff,et al.  Selective stimulation of T helper 2 cytokine responses by the anti‐psoriasis agent monomethylfumarate , 1996, European journal of immunology.

[28]  H. Thio,et al.  Long‐term systemic therapy with dimethylfumarate and monoethylfumarate (Fumaderm®) in psoriasis , 1995 .

[29]  P. Frosch,et al.  Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. , 1994, Journal of the American Academy of Dermatology.

[30]  D. N. Kolbach,et al.  Fumaric acid therapy in psoriasis: results and side effects of 2 years of treatment. , 1992, Journal of the American Academy of Dermatology.

[31]  P. Spiegel,et al.  [Osteomalacia as an apparently rare side effect of oral fumaric acid therapy. Secondary DeToni-Debré Fanconi syndrome in the adult]. , 1992, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[32]  J. Hermans,et al.  Fumaric acid therapy for psoriasis: a randomized, double-blind, placebo-controlled study. , 1990, Journal of the American Academy of Dermatology.

[33]  C. Nieboer,et al.  Fumaric acid therapy in psoriasis: a double-blind comparison between fumaric acid compound therapy and monotherapy with dimethylfumaric acid ester. , 1990, Dermatologica.

[34]  C. Nieboer,et al.  Systemic therapy with fumaric acid derivates: new possibilities in the treatment of psoriasis. , 1989, Journal of the American Academy of Dermatology.

[35]  J. Roodnat,et al.  [Acute kidney insufficiency in patients treated with fumaric acid esters for psoriasis]. , 1989, Nederlandsch tijdschrift voor geneeskunde.

[36]  W SCHWECKENDIEK,et al.  [Treatment of psoriasis vulgaris]. , 1959, Medizinische Monatsschrift.