Papp 2012

Methods	RCT, placebo‐controlled, double‐blind trial Date of study: December 2009–April 2010 Location: 23 centres worldwide
Participants	Randomised: 198 participants (mean age 42 years, 107 male) Inclusion criteria Participants with moderate‐severe psoriasis PASI ≥ 12, BSA > 10% Age 18‐70 years Exclusion criteria Pregnancy, immunosuppression Had past history of malignant tumours Dropouts and withdrawals 10/198 (5%) Brodalumab 70: ineligible (1) Brodalumab 140: decision (1) Brodalumab 210: (3): deviation (1) consent withdrawn (1) decision (1) Brodalumab 280: (2): ineligible (1), AE (1) Placebo (3): ineligible (1), consent withdrawn (2)
Interventions	Intervention A. Brodalumab 70 (n = 39), SC, 70 mg, day 1‐weeks 1, 2, 4, 6, 8, 10, 10 weeks Control intervention B. Brodalumab 140 (n = 39), SC, 140 mg, day 1 and weeks 1, 2, 4, 6, 8, 10, 10 weeks C. Brodalumab 210 (n = 40), SC, 210 mg, day 1 and weeks 1, 2, 4, 6, 8, 10, 10 weeks D. Brodalumab 280 (n = 42), SC, 280 mg, day 1 and weeks 1, 2, 4, 6, 8, 10, 10 weeks E. Placebo (n = 38), SC, day 1 and weeks 1, 2, 4, 6, 8, 10, 10 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI75 Secondary outcomes of the trial PASI 50/90/100 at week 12 BSA PGA DLQI AEs
Notes	Funding source, quote (p 1182): "The study was funded by Amgen" Declarations of interest (p 1188‐89): "Dr. Papp reports receiving consulting fees from Abbott, Amgen, Astellas, Celgene, Centocor, Eli Lilly, Galderma, Graceway Pharmaceuticals, Janssen, Johnson & Johnson, Merck, Norvartis, Pfizer, and UCB, lecture fees from Abbott, Amgen, Astellas, Celgene, Centocor, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, and Stiefel, and grant support from Abbott, Amgen, Astellas, Celgene, Centocor, Eli Lilly, Galderma, Glaxo‐SmithKline, Graceway Pharmaceuticals, Janssen, Johnson & Johnson, Medimmune, Merck, Novartis, Pfizer, Stiefel, and UCB; Dr. Leonardi, receiving consulting fees from Abbott, Amgen, Centocor, Eli Lilly, and Pfizer, lecture fees from Abbott and Amgen, and investigator fees from Abbott, Amgen, Celgene, Centocor, Galderma, GlaxoSmithKline, Incyte, Maruho, Novartis, Novo Nordisk, Pfizer, Schering‐Plough (now Merck), Sirtris, Stiefel, Vascular Biogenics, and Wyeth (now Pfizer); Dr. Menter, receiving consulting fees from Abbott, Amgen, Astellas, Centocor, Galderma, Genentech, and Wyeth, lecture fees from Abbott, Amgen, Centocor, Galderma, and Wyeth, and fees for expert testimony from Galderma; Dr. Krueger, receiving consulting fees from Centocor, Eli Lilly, and Pfizer and grant support from Amgen, Centocor, Eli Lilly, Merck, and Pfizer; and Drs. Krikorian, Aras, Li, Russell, Thompson, and Baumgartner being full‐time employees of Amgen. No other potential conflict of interest was relevant to this article was reported."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (protocol p 30): “Randomization: IVRS will be used to randomise subjects into the study. The randomisation list will be generated by Amgen using a permuted block design within each of 4 strata based on BMI at baseline, and participation in the PK study” Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (protocol p 30): “Randomization: IVRS will be used to randomise subjects into the study. Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (protocol p 24 & 50): “double‐blind placebo controlled... Subjects randomised to active drug will receive additional placebo injections as necessary to maintain the blind” Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (protocol p 39): "PASI assessments will be performed by a blinded assessor. The blinded assessor will be a healthcare professional who has been certified as trained with the standard PASI" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	198 included/198 analysed Quote (p 1183): "The analyses of efficacy endpoints were performed on data from all patients who underwent randomisation (full set analysis), according to the intention‐to‐treat principle... Missing data were handled by means of the baseline‐value‐carried‐forward method or the imputation of no response" Comment: probably done
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT00307437). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported.