Gordon UNCOVER‐1, 2016

Methods	RCT, placebo‐controlled, double blind Date of study: November 2011‐June 2014 Location: multicentre (104) in Europe, Australia, North America
Participants	Randomised: 1296 participants (mean age 45 years, 883 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 12 or BSA ≥ 10), age ≥ 18 years Exclusion criteria Pregnancy, immunosuppression, kidney insufficiency, liver insufficiency, past history of malignant tumours, active infection, uncontrolled cardiovascular disorder, uncontrolled diabetes, uncontrolled hypertension Had received anti IL17 Dropouts and withdrawals 66/1296 (5%); Ixekizumab 4‐week group (24), ixekizumab 2‐week group (18), placebo (24) AEs: ixekizumab 4‐week group (10), ixekizumab 2‐week group (10), placebo (6) Protocol violation: ixekizumab 4‐week group (6), ixekizumab 2‐week group (0), placebo (3) Participant decision: ixekizumab 4‐week group (6), ixekizumab 2‐week group (5), placebo (6) Lost to follow‐up: ixekizumab 4‐week group (0), ixekizumab 2‐week group (2), placebo (1) Investigator decision: ixekizumab 4‐week group (1), ixekizumab 2‐week group (1), placebo (1) Lack of efficacy: ixekizumab 4‐week group (1), ixekizumab 2‐week group (0), placebo (7)
Interventions	Intervention A. Ixekizumab (n = 432), SC, 80 mg, 2 injections week 0, 1 injection monthly Control intervention B. Ixekizumab (n = 433), SC, 80 mg, 2 injections week 0, 1 injection eow C. Placebo (n = 431), SC
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PGA 0‐1 PASI 75 Secondary outcomes of the trial PASI 90 DLQI NAPSI AEs
Notes	Funding source: Quote (p 346): “The trials were sponsored by Eli Lilly and were designed by the scientific steering committee and Eli Lilly personnel. The site investigators collected the data, Eli Lilly personnel performed the data analyses, and all the authors had access to the data.” Declarations of interest (p 355): "Disclosure forms provided by the authors are available with the full text of this article at NEJM.org." Gordon received grants and personal fees from Abbvie, Amgen, Celgene, Eli Lilly, Novartis; and personal fees from Pfizer and Medac.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (supplemental appendix): “Patients were assigned to treatment groups as determined by a computer‐generated random sequence .." Comment: clearly defined
Allocation concealment (selection bias)	Low risk	Quote (supplemental appendix): “Patients were assigned to treatment groups as determined by a computer‐generated random sequence using an interactive voice response system (IVRS). Site personnel confirmed that they had located the correct assigned investigational product package by entering a confirmation number found on the package into the IVRS” Comment: clearly defined
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 346): “double‐blind, placebo‐controlled” Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 346): “double‐blind, placebo‐controlled” Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 1296, analysed 1296 Management of missing data: Quote (p 348): “Unless otherwise specified, all analyses of efficacy during the induction period were performed according to the intention‐to‐treat principle. Missing values for the PASI and the sPGA score were imputed conservatively as nonresponses, regardless of the reason for the missing data” Comment: probably done
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01474512). The pre‐specified outcomes mentioned in the protocol and in the methods section appeared to have been reported.