Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments

Abstract

SummaryFumaric 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.

Long‐term real‐life safety profile and effectiveness of fumaric acid esters in psoriasis patients: a single‐centre, retrospective, observational study

“…A retrospective case series reported that 26% of psoriasis patients (16/62) had a lymphocyte count <500/μL . Usually, these phenomena are transient and reversible and may serve as a biomarker for drug efficacy of FAEs . The changes in leucocyte and lymphocyte counts observed in the present study (Table ) compare well with those recently reported by Sondermann et al .…”

“…A clinically relevant increase in liver enzymes was observed in up to 5% of patients (Table ); increases were reversible after FAE dose reduction or treatment discontinuation. Mild‐to‐moderate elevations in liver enzymes (below twice the upper limit of normal) were reported in up to 40% of psoriasis patients taking FAEs but rarely necessitated discontinuation of therapy . To date, no animal or human data have indicated any risk of permanent liver damage with FAE use.…”

Renal dysfunction in patients taking fumaric acid esters – a retrospective cross‐sectional study

“…One large meta‐analysis has shown similar response rates to the TNF analogue etanercept . A recent Cochrane review has shown that FAE are comparable to methotrexate in terms of efficacy …”

Dimethyl fumarate (DMF) vs. monoethyl fumarate (MEF) salts for the treatment of plaque psoriasis: a review of clinical data

“…FAEs are used frequently in Germany and are available and used off-label in a number of other countries [6, 11, 12, 16, 33]. The significance of FAEs in the management of psoriasis is acknowledged by the Cochrane Collaboration [5] and by European and US official guidelines [3, 33, 34]. …”