Leonardi 2003

Methods	RCT, placebo‐controlled, double‐blind trial Date of study: December 2001‐April 2002 Location: 47 centres in USA
Participants	Randomised: 672 participants (mean age 45 years, 672 male) Inclusion criteria Participants with moderate‐severe stable plaque psoriasis, BSA > 10% Age ≥ 18 Quote (p 2015) “Had previously received phototherapy or systemic psoriasis therapy at least once or had been candidate to such therapy” Exclusion criteria Had received biologics treatments Had an active infection Had past history of malignant tumours Dropouts and withdrawals 103/672 (15.3%) Not received any treatment: etanercept LD (9), etanercept MD (5), etanercept HD (4), placebo (2) AEs: etanercept LD (8), etanercept MD (7), etanercept HD (5), placebo (8) Loss to follow‐up: etanercept LD (4), etanercept MD (4), etanercept HD (3), placebo (3) Lack of efficacy: etanercept LD (6), etanercept MD (2), etanercept HD (3), placebo (6) Patient refusal: etanercept LD (3), etanercept MD (4), etanercept HD (1), placebo (4) Protocol violation: etanercept LD (3), etanercept MD (4), etanercept HD (0), placebo (1) Death: etanercept LD (1), etanercept MD (1), etanercept HD (0), placebo (0) Unknown/other: etanercept LD (1), etanercept MD (0), etanercept HD (1), placebo (0)
Interventions	Intervention A. Etanercept LD (n = 169), SC auto‐administered, 25 mg, once/week, 12 weeks Control intervention B. Etanercept MD (n = 167), SC auto‐administered, 25 mg, twice/week, 12 weeks C. Etanercept HD (n = 168), SC auto‐administered, 50 mg, twice/week, 12 weeks D. Placebo (n = 168), SC, 12 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial PASI 50 PASI 90 DLQI PGA Safety Patient global assessment of psoriasis
Notes	Funding source, quote (p 2021): "Supported by Immunex, Seattle, a wholly‐owned subsidiary of Agen, Thousand Oaks, Calif" Declarations of interest (p 2021): "Drs. Leonardi, Powers, Goffe, and Gottlieb report having served as consultants for Amgen, and Drs. Leonardi, Goffe, and Gottlieb report having served as paid lecturers for Amgen. Dr. Gottlieb reports having served as a consultant and paid lecturer for Johnson & Johnson, Genentech, and Biogen; Dr. Leonardi reports having served as a consultant and paid lecturer for Johnson & Johnson and Genentech; Dr. Powers reports having served as a consultant for Genentech and Biogen; and Dr. Goffe reports having served as a consultant and paid lecturer for Biogen. Dr. Zitnik and Ms. Wang report owning equity in Amgen."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 2016): "Patients underwent central randomisation with the use of a permuted block randomisation list, with equal allocation to each of the four treatment groups" Comment: probably done
Allocation concealment (selection bias)	Low risk	Comment: no description of the method used to guarantee the allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 2015): "Double‐blind... Etanercept ... was supplied to patients in syringes, each containing the contents of one reconstituted vial of etanercept or matching placebo...All patients received two injections per dose of study" Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 2015): "Double‐blind... Etanercept ... was supplied to patients in syringes, each containing the contents of one reconstituted vial of etanercept or matching placebo...All patients received two injections per dose of study" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	672 randomised participants, 652 analysed (20 participants did not receive the treatment and were excluded from the analyses) Comment: modified ITT but number of participants not receiving treatment and not included in the analysis low and comparable between groups
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available. The pre‐specified outcomes mentioned in the methods section appeared to have been reported