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Impact of fumaric acid esters on cardiovascular risk factors and depression in psoriasis: a prospective pilot study

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Abstract

Patients with psoriasis have an increased risk of cardiovascular disease that is partly attributable to chronic systemic inflammation. The aim of our prospective pilot study was to investigate the impact of fumaric acid esters (FAE), a first-line systemic antipsoriatic treatment in Germany, on cardiovascular risk parameters. Participants with moderate-to-severe psoriasis from the University Medical Center Mannheim and the University Hospital Würzburg were treated with FAE for 16 weeks according to standard dosage recommendations. Disease severity, life quality and depression scores as well as biomarkers of inflammation, lipid and glucose metabolism were assessed prior to initiation of FAE and after 16 weeks. Out of 39 participants recruited, 27 completed the study. 44 % of all participants and 63 % of those completing the 16-week treatment achieved PASI 50 response and 27 or 37 % PASI 75 response. Clinical improvement was paralleled by significant improvement in quality of life, high treatment satisfaction and significant reduction of depressive symptoms. Adverse events, most frequently mild gastrointestinal complaints, flush and lymphocytopenia occurred in 89 %. FAE did not modify glucose metabolism or inflammatory parameters substantially. However, a highly significant increase in serum levels of the atheroprotective cytokine adiponectin was noted after 16 weeks (median 4.7 vs. 8.9 µg/ml; p = 0.0002). Our study demonstrates a significant beneficial impact of FAE on adiponectin, indicating a potential cardioprotective effect. It will be interesting to verify this finding in larger cohorts and to assess the long-term influence of FAE on cardiovascular risk and disease.

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Acknowledgments

Ms. Anette Oberst (Department of Dermatology, Venerology and Allergology, University Medical Center Mannheim) is acknowledged for excellent support with data documentation. Furthermore, we thank the medical doctors and nursing staff of our psoriasis clinics for help with patient recruitment. This work was supported in part by a Olympia Morata grant from the University of Heidelberg to AS, by grants of the Deutsche Forschungsgemeinschaft (DFG), SFB938, project H to SG, and by the young scientists’ program of the German network “Health Services Research Baden-Württemberg” of the Ministry of Science, Research and Arts in collaboration with the Ministry of Employment and Social Order, Family, Women and Senior Citizens, Baden-Württemberg (grant to MLS).

Conflict of interest

Dr. Schmieder conducted clinical trials for Abbvie and Pfizer and obtained support for conferences from Abbvie, Janssen-Cilag and Pfizer. Dr. Meyer-Schraml performed clinical trials for Abbvie, Merck, Novartis and Eli Lilly and was supported for participation in conferences by Abbvie. Dr. Schaarschmidt conducted clinical trials for Abbvie, Merck and Eli Lilly and received financial support for participation in conferences from Abbvie, ALK-Abello, Biogen Idec, Janssen-Cilag and MSD. Dr. Benoit conducted clinical trials for Almirall, Eli Lilly, LEO Pharma and Novartis; and received honoraria from Abbvie and Roche. Dr. Bauer performed clinical trials for Biogen Idec, Celgene, Eli Lilly, GSK, Merck, Novartis, Pfizer and Schering-Ploch; is member of an advisory board of MSD and obtained honoraria from MSD. Ms. Schmid served as study coordinator for clinical trials sponsored by Allmiral, Biogen Idec, BMS, Eli Lilly, GSK, LEO Pharma, Novartis and Roche. Prof. Goebeler is an advisory board member of MSD and served as investigator for Barrier Pharmaceutics, Johnson and Johnson, MSD, Novartis, Wyeth/Pfizer and Vicuron. He obtained honoraria from Galderma, La Roche-Posay und Serono. Prof. Goerdt received honoraria as Editor-in-Chief of the Journal of the German Dermatological Society (JDDG) and support for conferences from Abbvie, ALK-Abello, Alma Lasers, ARC Lasers, Asclepion, BMS, GSK, Janssen-Cilag, L’Oreal, LEO Pharma, Medac, Merck, MSD, Novartis, P&M Cosmetics, Pfizer and Roche. Prof. Peitsch served as investigator for Abbvie, Eli Lilly, Janssen-Cilag, Merck, Novartis and Pfizer; was member of an advisory board of MSD and Novartis; obtained honoraria from ALK-Abello, Abbvie, Janssen-Cilag, MSD and Novartis; and received support for conferences from Abbvie, ALK-Abello, Alma Lasers, ARC Lasers, Asclepion, BMS, GSK, Janssen-Cilag, L’Oreal, LEO Pharma, Medac, Merck, MSD, Novartis, P&M Cosmetics, Pfizer and Roche. Mr. Poppe, Dr. Hametner and PD Dr. Findeisen have no conflicts of interest relevant to this manuscript. The study presented here was not supported by pharmaceutical companies.

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    Authors and Affiliations

    1. Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany

      Astrid Schmieder, Manuel Poppe, Hanna Meyer-Schraml, Marthe-Lisa Schaarschmidt, Sergij Goerdt & Wiebke K. Ludwig-Peitsch

    2. Department of Neurology, University of Heidelberg, Heidelberg, Germany

      Christian Hametner

    3. Institute of Clinical Chemistry, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany

      Peter Findeisen

    4. Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany

      Sandrine Benoit, Boris Bauer, Sybille Schmid & Matthias Goebeler

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    1. Astrid Schmieder
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    A. Schmieder and M. Poppe contributed equally to this work.

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    Schmieder, A., Poppe, M., Hametner, C. et al. Impact of fumaric acid esters on cardiovascular risk factors and depression in psoriasis: a prospective pilot study. Arch Dermatol Res 307, 413–424 (2015). https://doi.org/10.1007/s00403-015-1541-7

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