AMAGINE‐3 2015.

Study characteristics
Methods	RCT, active/placebo‐controlled, double‐blind Date of study: September 2012 ‐ August 2014 Location: 142 centres worldwide (no sites that were included in the AMAGINE‐2 study)
Participants	Randomised: 1881 participants (mean age 45 years, 1288 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 12, PGA 3‐5, BSA ≥ 10), age 18 ‐ 75 years Exclusion criteria Pregnancy Active infection, past history of malignant tumours, active infection, kidney or liver insufficiency, uncontrolled cardiovascular disorder, uncontrolled diabetes, uncontrolled hypertension Had Crohn's disease Had used ustekinumab and/or anti‐IL17 biologic therapy Dropouts and withdrawals 65/1881 (3.4%): brodalumab 140 group (25), brodalumab 210 group (16), ustekinumab 45/90 group (10), placebo group (14) Ineligibility determined: brodalumab 140 group (3), brodalumab 210 group (0), ustekinumab 45/90 group (1), placebo group (2) AEs: brodalumab 140 group (4), brodalumab 210 group (4), Usk 45/90 group (1), placebo group (0) Lost to follow‐up: brodalumab 140 group (5), brodalumab 210 group (5), ustekinumab 45/90 group (3), placebo group (1) Full consent withdrawal: brodalumab 140 group (7), brodalumab 210 group (5), ustekinumab 45/90 group (3), placebo group (7) Other: brodalumab 140 group (6), brodalumab 210 group (2), ustekinumab 45/90 group (2), placebo group (4)
Interventions	Intervention A. Brodalumab (n = 629), SC, 140 mg (2 injections week 0, 1 injection eow) Control intervention B. Brodalumab (n = 624), SC, 210 mg (2 injections week 0, 1 injection eow) C. Ustekinumab (n = 313), SC, 45/90 mg (week 0, week 4 and every 12 weeks) D. Placebo (n = 315), orally (same drug administration)
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 PGA 0/1 (brodalumab compared to placebo) % of participants who had a 100% reduction in PASI score Secondary outcomes of the trial Improvement in PASI PGA score Participant‐reported outcome AEs
Notes	Funding source: Quote (p 1319) “Amgen funded both studies. ... and Amgen conducted the data analyses. All the authors interpreted the data” Declarations of interest (p 1327): "Disclosure forms provided by the authors are available with the full text of this article at NEJM.org." Dr. Lebwohl reports grant support from Amgen, AbbVie, Janssen Biotech, UCB Pharma, Pfizer, Celgene, Eli Lilly, and Novartis outside the submitted work.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (protocol): “The randomisation lists will be generated by Amgen using a permuted block design within each strata..." Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (protocol): “The randomisation lists will be generated by Amgen using a permuted block design within each strata...via an interactive voice response system” Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (protocol, cf 6. Treatment procedure): “This is a double dummy procedure...” Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (protocol, cf 6. Treatment procedure): "This is a double dummy procedure...”
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 1881, analysed 1881 Dealing with missing data Quote (protocol and p 1321) "...with missing data imputed as indicating no response" Comment: well described
Selective reporting (reporting bias)	High risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01708629) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported, except for participant‐reported outcome