Treatment of psoriasis with fumaric acid esters (Fumaderm<sup>®</sup>)

Mrowietz, Ulrich; Altmeyer, Peter; Bieber, Thomas; Röcken, Martin; Schopf, R. E.; Sterry, Wolfram

doi:10.1111/j.1610-0387.2007.06346.x

Cited by 62 publications

(69 citation statements)

References 7 publications

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“…Consequently, oxidized glutathione is converted into glutathione and will also be depleted by dimethylfumarate [1][2][3]. Nevertheless, the mechanisms of action of FAE in psoriasis are not completely understood [1]. Realistically, about 70% of psoriasis patients achieve psoriasis area and severity index (PASI) 50 or higher improvement within 3 months of treatment with FAE [1,4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the mechanisms of action of FAE in psoriasis are not completely understood [1]. Realistically, about 70% of psoriasis patients achieve psoriasis area and severity index (PASI) 50 or higher improvement within 3 months of treatment with FAE [1,4,5]. It is well known, however, that FAE are linked to high variability in treatment efficacy and adverse events [1].…”

Section: Introductionmentioning

confidence: 99%

“…Work from clinical studies and translational science carried out in patients with psoriasis initially pointed toward a major role of T lymphocytes as inducers of the disease phenotype. The pathogenic contribution of T lymphocytes has now been tested through clinical studies in a variety of immunosuppressive and immune-modifying agents in patients with psoriasis [1]. Fumaderm, an enteric-coated tablet containing fumaric acid esters (FAE) such as dimethylfumarate and calcium, magnesium and zinc salts of monoethylfumarate, has become a commonly used systemic psoriasis therapy in European countries such as Germany, the Netherlands and the UK [1].…”

Section: Introductionmentioning

confidence: 99%

“…The pathogenic contribution of T lymphocytes has now been tested through clinical studies in a variety of immunosuppressive and immune-modifying agents in patients with psoriasis [1]. Fumaderm, an enteric-coated tablet containing fumaric acid esters (FAE) such as dimethylfumarate and calcium, magnesium and zinc salts of monoethylfumarate, has become a commonly used systemic psoriasis therapy in European countries such as Germany, the Netherlands and the UK [1]. Dimethylfumarate is rapidly hydrolysed by esterases into monomethylfumarate, which is considered the active metabolite [2].…”

Section: Introductionmentioning

confidence: 99%

“…Dimethylfumarate depletes glutathione by the formation of covalently linked conjugates with glutathione. Consequently, oxidized glutathione is converted into glutathione and will also be depleted by dimethylfumarate [1][2][3]. Nevertheless, the mechanisms of action of FAE in psoriasis are not completely understood [1].…”

Section: Introductionmentioning

confidence: 99%

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Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Gambichler

Susok

Zankl

et al. 2016

Pharmacogenetics and Genomics

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Fumaric acid esters (FAE) are beneficial in the treatment of psoriasis. However, about a third of psoriasis patients do not respond to FAE. We aimed to determine whether glutathione-S-transferase (GST) M1 and GSTP1 polymorphisms are associated with treatment outcome in psoriasis patients treated with FAE. We studied 84 psoriasis patients who were treated with FAE for 3 months. FAE nonresponders were defined as having psoriasis area and severity improvement index less than 50% after 3-month therapy. GSTM1 genotyping for gene deletion and GSTP1 exon 5 105 Ile→Val polymorphisms were assessed using a high-resolution melting analysis. A dropout rate of 23.8% (20/84) was found; 25% (16/64) were FAE nonresponders. We observed 42 (84/50%) patients with G 9STM1*0 homozygous alleles and 42 (84/50%) patients with one or two active GSTM1 alleles. The Ile/Ile GSTP1 genotype was observed in 37 (84/44%), the Ile/Val GSTP1 genotype in 38 (84/45.2%) patients and the Val/Val GSTP1 genotype in nine (84/10.7%) patients. There was no significant (P>0.05) association between the GST genotypes assessed and the frequency FAE responder status, except for the Val/Val GSTP1 polymorphism, which was a significant (overall model fit; P=0.0012) predictor for nonresponders with an odds ratio of 43.4 (95% confidence interval: 4.2-511.1). The coefficient of regression was 3.9, with a SE of 1.2 as assessed by logistic regression analysis (P=0.0017). The Val/Val GSTP1 polymorphism predicts nonresponders in FAE treatment of psoriasis patients and may therefore serve as a biomarker that enables a laboratory-based pretreatment selection of patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Gambichler

Susok

Zankl

et al. 2016

Pharmacogenetics and Genomics

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Overcoming obstacles to repurposing for neurodegenerative disease

Shineman

Alam²,

Anderson³

et al. 2014

Ann Clin Transl Neurol

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Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments to patients but is also fraught with significant commercial, regulatory, and reimbursement challenges. The Alzheimer’s Drug Discovery Foundation (ADDF) and the Michael J. Fox Foundation for Parkinson’s Research (MJFF) convened an advisory panel in October 2013 to understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegenerative diseases. Here, we present opportunities on how philanthropy, industry, and government can begin to address these challenges, promote policy changes, and develop targeted funding strategies to accelerate the potential of FDA-approved repurposed drugs.

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Determination of dimethyl fumarate in desiccant and antimould sachets by reversed-phase liquid chromatography

Gennari

Montesano

Salzano³

et al. 2011

Biomed. Chromatogr.

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A method for the determination of dimethyl fumarate (DMF) in desiccant and antimould sachets, employed for protecting consumer products from humidity and mould, has been developed. The method is based on a solid-liquid extraction followed by HPLC-UV analysis. The method was validated with respect to recovery, linearity, limits of detection and quantitation and precision. The recovery was 98%. The correlation coefficient value (r) was equal to 0.94. Both intra- and inter-day precisions were studied at several concentration levels, being satisfactory in all cases (RSD < 5). Limits of detection and quantification values were in the low microgram per gram level, thus allowing the determination of DMF at concentrations below the limit established (0.1 mg/kg) by the recent EU Directive (Decision 2009/251/EC). The proposed procedure was applied for the determination of the target compound in 41 desiccant and antimould samples. DMF was detected in 39.0% of samples and its content in many samples exceeded the legal limits. The results of our analysis highlight the high risk of exposure to this powerful allergic sensitizer for consumers.

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Treatment of psoriasis with fumaric acid esters (Fumaderm^®)

Cited by 62 publications

References 7 publications

Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Overcoming obstacles to repurposing for neurodegenerative disease

Determination of dimethyl fumarate in desiccant and antimould sachets by reversed-phase liquid chromatography

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Treatment of psoriasis with fumaric acid esters (Fumaderm®)

Cited by 62 publications

References 7 publications

Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Val/Val glutathione-S-transferase P1 polymorphism predicts nonresponders in psoriasis patients treated with fumaric acid esters

Overcoming obstacles to repurposing for neurodegenerative disease

Determination of dimethyl fumarate in desiccant and antimould sachets by reversed-phase liquid chromatography

Contact Info

Product

Resources

About

Treatment of psoriasis with fumaric acid esters (Fumaderm^®)