Papp 2005.

Study characteristics
Methods	RCT, placebo‐controlled, double‐blind Date of study: not stated Location: 50 centres in USA, Canada and Western Europe
Participants	Randomised: 611 participants (mean age 45 years, male 382 out of 583 participants who received 1 dose) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 10, BSA ≥ 10%, age ≥ 18 years) Non‐response to topical treatment Only 1 previous systemic treatment allowed Exclusion criteria Kidney insufficiency, liver insufficiency Had received biologics (anti‐TNF) Had an active infection Dropouts and withdrawals 52/611 (8.5%) Placebo (26): refusal (7) eligibility (6) lost to follow‐up (6) AE (2) lack efficacy (4) protocol requirement (1) Etanercept 25 (13): refusal (5) eligibility (4) AE (3) lack efficacy (1) Etanercept 50 (13): refusal (5) eligibility (2) lost to follow‐up (3) AE (2) lack efficacy (1)
Interventions	Intervention A. Etanercept (n = 204), SC, 25 mg twice a week, 12 weeks Control intervention B. Etanercept (n = 203), SC, 50 mg twice a week, 12 weeks C. Placebo (n = 204), SC, twice a week, 12 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial Proportion of participants with PGA score of 0 or 1 at Week 12 PASI 50 at Week 12 PASI 90 at Week 12 Percentage improvement from baseline at week 12 to PASI AEs QoL
Notes	Funding source, quote (p 1304): "This study was supported by Immunex Corporation (Seattle, WA, U.S.A)" Declarations of interest: (p 1304) S.T. has received research support from Amgen; C.E.M.G. has been a paid consultant for Wyeth and Amgen; A.M.N and R.Z. are both full‐time employees of Amgen."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote (p 1305): "Patients were randomly assigned (using an Interactive Voice Response system) to receive placebo or etanercept) Comment: not stated
Allocation concealment (selection bias)	Low risk	Quote (p 1305): "Patients were randomly assigned (using an Interactive Voice Response system) to receive placebo or etanercept) Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 1305): “ the patients, study site personnel and all sponsor representatives remained blinded to the initial randomisation treatment groups...” Comment: placebo‐controlled, probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 1305): “ the patients, study site personnel and all sponsor representatives remained blinded to the initial randomisation treatment groups...” Comment: placebo‐controlled, probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	611 randomised participants, 583 analysed (28 participants did not receive the treatment and were excluded from the analyses) Sensitivity analysis (Table 2) were performed with the 611 randomised participants Management of missing data: Quote "In the analyses, missing post baseline efficacy data were imputed using last observation carried forward. In addition, a sensitivity analysis was performed on the binary efficacy endpoints to evaluate the robustness of the primary analysis. This sensitivity analysis included all randomised patients. In addition, rather than using LOCF imputation patients with missing data at a given visit were assumed to have not met the response criteria for that endpoint". Comment: the main result (primary outcome) was not an ITT analysis
Selective reporting (reporting bias)	High risk	Comment: no protocol was available. The prespecified outcomes mentioned in the Methods section appeared to have been reported except for the results of participant‐reported endpoints summarised in a separate publication