Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments. (29th August 2016)

• Record Type: Journal Article
• Authors: Atwan, A.; Ingram, J.R.; Abbott, R.; Kelson, M.J.; Pickles, T.; Bauer, A.; Piguet, V.
• Is Part Of: British journal of dermatology. Volume 175:Number 5(2016)
• Page Start: 873
• Page End: 881
• Publication Date: 2016-08-29
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.14676
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Fumaric acid esters (FAEs) are licensed for the treatment of moderate‐to‐severe psoriasis in Germany but are also used off‐label in many other countries. We conducted this systematic review to synthesize the highest‐quality evidence for the benefits and risks of FAEs for psoriasis. Our primary outcomes were change in Psoriasis Area and Severity Index score and dropout rates due to adverse effects. Randomized controlled trials (RCTs) of FAEs or dimethylfumarate were included, with no restriction on age or psoriasis subtype. We searched the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library, Medline, Embase, LILACS and five trials registers, and hand searched six conference proceedings. Six RCTs with a total of 544 participants were included, four of which were published only as abstracts or brief reports, limiting study reporting. Five RCTs compared FAEs with placebo, and all demonstrated benefit in favour of FAEs. However, meta‐analysis was possible only for PASI 50 response after 12–16 weeks, which was achieved by 64% of participants on FAEs compared with 14% on placebo: risk ratio (RR) 4·55, 95% confidence interval (CI) 2·80–7·40; two studies; 247 participants; low‐quality evidence). There was no difference in dropout rates due to adverse effects (RR 5·36, 95% CI 0·28–102·12; one study; 27 participants; very low‐quality evidence and wide CI). More participants experienced nuisance adverse effects with FAEs (76%) than with placebo (16%) (RR 4·72, 95% CI 2·45–9·08; one study; 99 participants; moderate‐quality evidence), mainly abdominal pain, diarrhoea and flushing. One head‐to‐head study of very low‐quality evidence comparing FAEs with methotrexate reported comparable efficacy and dropout rates, although FAEs caused more flushing. The evidence in this review was limited and must be interpreted with caution; studies with better design and outcome reporting are needed. Abstract : What's already known about this topic? Fumaric acid esters (FAEs) are licensed for the treatment of moderate‐to‐severe psoriasis in Germany, and are used off‐label in many other countries. Non‐Cochrane systematic reviews previously examined the effect of FAEs in psoriasis, but have not rigorously assessed the quality of the evidence. What does this study add? Six randomized controlled trials with 544 participants were included, four of which were published only as abstracts or brief reports, resulting in low‐ or very low‐quality evidence. Results suggest that FAEs are superior to placebo, but their efficacy in comparison with methotrexate is uncertain due to very low‐quality evidence. The relative risk of nuisance adverse effects with FAEs is about five times greater than with placebo; however, there is insufficient evidence available to give an accurate figure for dropout rates due to adverse effects. Linked Comment: Egeberg. Br J Dermatol 2016;175 :857 . Audio Commentary