title: Oral fumaric acid esters for psoriasis: abridged Cochrane systematic review including GRADE assessments.
abstract: 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.
authors.affiliation: Department of Dermatology & Wound Healing, Cardiff Institute of Infection & Immunity, Cardiff University, 3rd Floor Glamorgan House, Heath Park, Cardiff, CF14 4XN, U.K.
authors.forename: A
authors.initials: A
authors.lastname: Atwan
authors.affiliation: Department of Dermatology & Wound Healing, Cardiff Institute of Infection & Immunity, Cardiff University, 3rd Floor Glamorgan House, Heath Park, Cardiff, CF14 4XN, U.K.. ingramjr@cardiff.ac.uk.
authors.forename: J R
authors.initials: JR
authors.lastname: Ingram
authors.affiliation: Welsh Institute of Dermatology, University Hospital of Wales, Cardiff, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Abbott
authors.affiliation: South East Wales Trials Unit, Institute of Translation, Innovation, Methodology and Engagement, Cardiff University, Cardiff, U.K.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kelson
authors.affiliation: South East Wales Trials Unit, Institute of Translation, Innovation, Methodology and Engagement, Cardiff University, Cardiff, U.K.
authors.forename: T
authors.initials: T
authors.lastname: Pickles
authors.affiliation: Department of Dermatology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Department of Dermatology & Wound Healing, Cardiff Institute of Infection & Immunity, Cardiff University, 3rd Floor Glamorgan House, Heath Park, Cardiff, CF14 4XN, U.K.
authors.forename: V
authors.initials: V
authors.lastname: Piguet
mesh_terms: D000284:Administration, Oral; D003879:Dermatologic Agents / Q000008:administration & dosage*; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D003879:Dermatologic Agents; D005650:Fumarates; D010919:Placebos; D008727:Methotrexate