Fumaric acid esters for psoriasis: a systematic review.

BACKGROUND: Psoriasis is a chronic skin disease associated with increased morbidity and mortality. Effective and safe long term treatment options are required to manage the illness successfully. A number of systemic agents are available, however, each of them has potentially significant side effects. Fumaric acid esters (FAE) are used first line in Germany for the management of moderate to severe psoriasis, however, their use in Ireland is on an unlicensed basis (Clinical and Experimental Dermatology 37:786-801, 2012).

OBJECTIVES: The purpose of this literature review is to evaluate the efficacy and safety of FAEs in the management of moderate to severe psoriasis in adult patients. The reviewer intends to systematically review all available literature on the efficacy and/or safety of fumaric acid esters in the management of moderate to severe psoriasis in adult patients.

METHODS: A systematic review of the literature was performed by one reviewer. The PubMed, TRIP, Embase, and Cochrane Collaboration databases were systematically interrogated to include randomised controlled trials, cohort studies and case studies evaluating the efficacy and/or safety of FAEs in the management of moderate to severe psoriasis in adult patients. Inclusion criteria were studies which included adults over 18 years of age, with a diagnosis of moderate to severe chronic plaque psoriasis, who were treated with FAEs and no other systemic anti-psoriatic agents concurrently. Exclusion criteria were studies involving children, mild psoriasis, studies which did not include patients with chronic plaque psoriasis, the use of FAE for the management of illnesses other than psoriasis, and patients treated with more than one systemic anti-psoriatic agent concurrently.

RESULTS: In total 19 articles were selected for review including 2 randomised placebo controlled trials, 1 non-randomised comparative study, 7 retrospective cohort studies, 2 prospective cohort studies and 7 case studies. The findings suggest that FAEs are a safe and effective treatment option for the management of moderate to severe psoriasis in adult patients. Gastrointestinal side effects may occur on treatment initiation and may be minimised by slow dose titration. Lymphocytopenia and eosinophilia are common, however, they are rarely of significance and there is no high level of evidence available to suggest a resultant increased risk of infection or malignancy. Rarely alterations of renal and hepatic function may occur, however, these are largely reversible on treatment withdrawal.

CONCLUSION: In conclusion, the use of FAE in the management of moderate to severe psoriasis is a promising treatment option, especially for those patients intolerant of, or unresponsive to other agents. If blood parameters are closely monitored during treatment as per the European Medicine Agencies guidelines (European Medicines Agency, 'Updated recommendations to minimise the risk of the rare brain infection PML with Tecfidera', https://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/10/WC500196017.pdf , 2015) they may be safely used in practice. The licensing of FAEs in Ireland for the treatment of moderate to severe psoriasis would be desirable, increasing available treatment options.