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Dimethylfumarate for Psoriasis

Pronounced Effects on Lesional T-Cell Subsets, Epidermal Proliferation and Differentiation, but not on Natural Killer T Cells in Immunohistochemical Study

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Abstract

Background: T-cell infiltration, epidermal hyperproliferation, and disturbed keratinization are pathologic hallmarks of plaque psoriasis. Oral fumaric acid esters are an effective therapy for psoriasis and are believed to exert their effects mainly through their anti-inflammatory properties.

Objective: To investigate the differential effects of dimethylfumarate (BG-12; FAG-201) for psoriasis on lesional T-cell subsets, natural killer (NK) T cells, and keratinocyte hyperproliferation and differentiation.

Study Design: A before-and-after clinical and immunohistochemical study as part of a larger clinical trial.

Setting: Single outpatient clinic.

Patients: Six patients with moderate-to-severe psoriasis.

Intervention: Dimethylfumarate 720mg daily for 16 weeks.

Methods: Biopsies were taken from the lesional skin of six psoriatic patients, at baseline and after 16 weeks of treatment with dimethylfumarate. Clinical severity scores were obtained (Psoriasis Area Severity Index [PASI] and psoriasis severity SUM scores). T-cell subsets (CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+), cells expressing NK receptors (CD94, CD161), an epidermal proliferation marker (Ki67), and a keratinization marker (K10) were immunohistochemically stained and, together with ‘epidermal thickness,’ quantified using image analysis.

Results: At week 16, the mean PASI and SUM scores were reduced by 55% (p < 0.01) and 49% (p < 0.01), respectively. In line with these results, epidermal hyperproliferation, keratinocyte differentiation, and epidermal thickness significantly improved. In the dermis and the epidermis, the relevant T-cell subsets significantly declined. However, in both the lesional psoriatic dermis and epidermis, cells expressing NK receptors (CD94 and CD161) persisted after 16 weeks of treatment.

Conclusions: Dimethylfumarate is an effective therapy for moderate-to-severe plaque psoriasis. The drug may act by reducing lesional T-cell subsets and normalizing epidermal hyperproliferation and keratinization, but does not reduce NKT cells.

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Acknowledgments

This study was part of a larger clinical trial by Fumapharm AG, which was funded. Prof. van de Kerkhof has acted as a consultant for Schering Plough, Cellgene, Centocor, Allmirall, UCB, Wyeth, Pfizer, Soffinova, Abbott, Actelion, Galderma, Novartis, Jansen Cilag, and Leo Pharma, and has carried out clinical trials for Centocor, Wyeth, Schering Plough, Merck Serono, Abbott, and Philips Lighting. The other authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Dermatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, NL-6500, HB Nijmegen, the Netherlands

    H. Jorn Bovenschen, Annechien M.G. Langewouters & Peter C.M. van de Kerkhof

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  1. H. Jorn Bovenschen
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  2. Annechien M.G. Langewouters
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  3. Peter C.M. van de Kerkhof
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Correspondence to H. Jorn Bovenschen.

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Bovenschen, H.J., Langewouters, A.M. & van de Kerkhof, P.C. Dimethylfumarate for Psoriasis. Am J Clin Dermatol 11, 343–350 (2010). https://doi.org/10.2165/11533240-000000000-00000

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