Gottlieb 2012.

Study characteristics
Methods	RCT, placebo‐controlled, double‐blind Date of study: November 2010 – December 2011 Location: Multicentre in Boston, USA
Participants	Randomised: 478 participants (methotrexate: mean age 43 years and 153 male; placebo: mean age 45 years and 167 male) Inclusion criteria Participants with moderate‐severe psoriasis (author assessment ≥ 6 months or PASI ≥ 10 or BSA ≥ 10%), age ≥ 18 years Non‐response to topical treatment Exclusion criteria Kidney insufficiency, liver insufficiency Had received biologics Had received conventional systemic treatments Dropouts and withdrawals 61/478 (12.8%) Methotrexate 28/239 (11.7%); placebo 33/239 (13.8%) Time and reasons : Methotrexate: AE (10), lost to follow‐up (5), ineligibility (4), noncompliance (4), full consent withdrawn (4) Placebo: AE (5), lost to follow‐up (9) ineligibility (2), noncompliance (7), disease progression (3), full consent withdrawn (5), other (2)
Interventions	Intervention A. Methotrexate (n = 239), orally, 15 mg/week 7.5 mg ‐ 10 mg to a maximum of 15 mg, 24 weeks + etanercept, SC, 50 mg x 2/weeks, S1 ‐ S12 and 50 mg/week, S12 ‐ S24, 24 weeks Control intervention B. Placebo (n = 239), orally, 24 weeks + etanercept, SC, 50 mg x 2/weeks, S1 ‐ S12 and 50 mg/week, S12 ‐ S24, 24 weeks
Outcomes	Assessments at 24 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial PASI 75 at 12 weeks PASI 50 at 12 weeks PASI 50 at 24 weeks PASI 90 at 12 weeks PASI 90 at 24 weeks PGA at 12 weeks and 24 weeks BSA at 12 and 24 weeks AEs Change of laboratory assessment
Notes	Funding source, quote (p 649): "This study was funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer..." Declarations of interest (Appendix): "A.B.G. is a consultant and/or advisory board member for Abbott, Actelion, Amgen, Astellas, Beiersdorf, Bristol‐Myers Squibb, Can‐Fite, Celgene, Centocor (Janssen), Dermipsor, Incyte, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, TEVA, and UCB and is a recipient of research/educational grants paid to Tufts Medical Center by Abbott, Amgen, Celgene, Centocor (Janssen), Immune Control, Novartis, Novo Nordisk, Pfizer, and UCB. R.G.L. has served as an investigator, on the scientific advisory board, and speaker for Abbott, Amgen, Centocor, and Pfizer, and as an advisor and investigator for Celgene, Novartis, and Johnson & Johnson. B.E.S. has served as an advisor, consultant, investigator, and speaker for Abbott, Amgen, and Centocor, and as an advisor, consultant, and investigator for Celgene, Novartis, Maruho, and Pfizer. K.A.P. has been a consultant, advisory board member, and investigator for Abbott, Amgen, Celgene, Centocor, Janssen‐Ortho, MedImmune, Merck, Pfizer, Schering‐Plough, and Wyeth (Wyeth was acquired by Pfizer in October 2009); has consulted for Astellas and UCB; and has served as a speaker for Abbott, Amgen, Celgene, Janssen‐Ortho, Pfizer, Schering‐Plough, and Wyeth. P.K., K.C., E.H.Z.T., M.H., and G.K. are employees and stockholders of Amgen Inc."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote (p 650): "This was a randomised..." Comment: no description of the method used to guarantee random sequence generation
Allocation concealment (selection bias)	Unclear risk	Quote (p 650): "This was a randomised...study" Comment: no description of the method used to guarantee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 650): “double‐blinded placebo‐controlled” Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 650): “double‐blinded placebo‐controlled” Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 478, analysed 478 Management of missing data: Quote (p 651): “Efficacy analyses were performed using the ITT set (all randomised patients)... Missing postbaseline data were imputed using last observation carried forward for primary analyses of all efficacy endpoints...” Comment: done
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01001208) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported