Tyring 2006.

Study characteristics
Methods	RCT, placebo‐controlled, double‐blind Date of study: June 2003 – January 2004 Location: 39 centres in Houston, USA and Canada
Participants	Randomised: 620 participants (mean age 46 years, 419 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 10, BSA ≥ 10), age > 18 years Exclusion criteria Kidney insufficiency, liver insufficiency, past history of malignant tumours Had received conventional systemic treatments Had received biologics (etanercept or anti‐TNF) Dropouts and withdrawals 23/620 (3.7%); etanercept group (6), placebo group (15) AEs: etanercept group (4), placebo group (3) Disease progression: etanercept group (1), placebo group (4) Withdrawal of consent: etanercept group (1), placebo group (5) Lost to follow‐up: placebo group (4) Non‐compliance: placebo group (1)
Interventions	Intervention A. Etanercept (n = 311), 50 mg, SC, twice weekly, 12 weeks Control intervention B. Placebo (n = 309), SC, twice weekly, 12 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial DLQI at 12w PASI 50 PASI 90 the 17‐item Hamilton rating scale for depression Beck depression inventory
Notes	Funding, Quote (p 361): "The study was designed by Immunex, S Tyring, and other members of the Etanercept Psoriasis study group (The complete data set was held at the central data‐processing facility at Amgen) Declarations of interest (pp 367‐8): "S Tyring has received research support from Amgen. A Gottlieb is a consultant for several companies (Amgen, BiogenIdec, CellGate, Centocor, Genentech, Novartis AG, Wyeth Pharmaceuticals, Schering‐Plough Corporation, Eisai, Celgene, Bristol Myers Squibb, Beiersdorf, Warner Chilcott, Abbott Labs, Allergan, Kemia, Roche, Sankyo, Medarex, Celera, TEVA, Actelion, and Advanced ImmuniT) and is on the speaker’s bureau for Amgen, BiogenIdec, and Wyeth Pharmaceuticals. She has also received research funding from Amgen, BiogenIdec, Centocor, Genentech, Abbott Labs, Ligand Pharmaceuticals, Beiersdorf, Fujisawa Healthcare, Celgene Corp, Synta, Bristol Myers Squibb, Warner‐Chilcott, and Paradigm. K Papp is a consultant, has received research funding, and has served as a speaker for Amgen, BiogenIdec, Centocor, Genentech, Novartis, Wyeth, Schering‐Plough, Abbott, Allergan, Medimmune, Serono, Xoma, Isotechnica, and GlaxoSmithKline. He has also served as a medical or scientific officer for Amgen, Centocor, Genentech, and Serono. K Gordon has received research support and honoraria from Abbott, Amgen, Biogen‐IDEC, Centocor, Genentech, and Synta. C Leonardi is: a consultant, investigator, and speaker for Amgen and Genentech and has received educational grants from these companies; a consultant, investigator, and speaker for Centocor; a consultant and investigator for Serono; and a consultant, investigator, and speaker for Abbott..."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 30): “Randomisation code lists were generated in the Biostatistics Department at Amgen by a designed person with no other association with the study” Comment: probably done
Allocation concealment (selection bias)	Unclear risk	Quote (p 30): “Randomisation code lists were generated in the Biostatistics Department at Amgen by a designed person with no other association with the study” Comment: no precision
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 30): "All patients received 2 injections per dose of investigational product” Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 30): “To prevent study assessors from being influenced by the presence of an injection site reaction, patients applied dressings to the last three injection sites and to any erythematous injection sites before each psoriasis evaluation” Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 620, analysed 617 for the primary outcome Management of missing data: quote (p 31): “The primary analyses for all efficacy endpoints included all randomised patients who received at least one dose of investigational product. Missing values were imputed using last observation carried forward” Comment: only 2 participants did not receive at least 1 dose, 618 participants should be involved in the mITT, however 617 participants were analysed for the primary outcome
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT00111449) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported