Efficacy, effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies

Summary Fumaric acid esters ( FAE s) are increasingly used as a systemic treatment for psoriasis, but there are still uncertainties regarding their suitability. The objective of this systematic review was to assess the evidence for the efficacy and safety of FAE s in psoriasis treatment. A systematic literature search was performed in seven databases up to 17 August 2015. Inclusion criteria were studies that reported clinical effects of FAE s in patients with psoriasis without restrictions in study design, language or publication date. Methodological quality of randomized controlled trials ( RCT s) and overall level of quality were assessed using the Cochrane risk of bias tool and the Grading of Recommendation, Assessment, Development and Evaluation approach, respectively. A total of 68 articles were included. There were seven RCT s (total 449 patients) that had an unclear risk of bias and were too clinically heterogeneous to allow a meta‐analysis. Overall, mean Psoriasis Area and Severity Index decreased by 42–65% following 12–16 weeks of treatment. There were 37 observational studies (a total of 3457 patients) that supported the RCT findings, but most were uncontrolled with a high risk of bias. Commonly reported adverse events included gastrointestinal complaints and flushing, leading to treatment withdrawal in 6–40% of patients. Several case‐reports described rare adverse events, such as renal Fanconi syndrome and progressive multifocal leukoencephalopathy. There was a lack of studies focusing on long‐term use and comparisons with other treatments. This review concluded that there is low‐quality evidence to recommend the use of oral FAE s to treat plaque psoriasis in adult patients. Studies focusing on long‐term safety and comparison with systemic psoriasis treatments could lead to a better understanding of the role of FAE s as a treatment for psoriasis.