Langley FIXTURE, 2014

Methods	RCT, active, placebo‐controlled, double‐blind trial Date of study: June 2011‐June 2013 Location: 231 centres worldwide (Fixture)
Participants	Randomised: 1306 participants, mean age 44 years, 929 male Inclusion criteria Participants with moderate‐severe psoriasis PASI ≥ 12, IGA 3‐4, BSA ≥ 10% Age ≥ 18 Non‐response to topical treatment Non‐response to phototherapy Non‐response to conventional systemic treatment Exclusion criteria Immunosuppression Had an active infection Had past history of malignant tumours Dropouts and withdrawals 73/1306 (5.6%) AEs: sekunimab 300 (4), sekunimab 150 (2), etanercept (6), placebo (2) Lack of efficacy: sekunimab 300 (0), sekunimab 150 (0), etanercept (2), placebo (9) Withdrew consent: sekunimab 300 (5), sekunimab150 (5), etanercept (5), placebo (10) Physician decision: sekunimab 300 (1), sekunimab 150 (2), etanercept (0), placebo (2) Protocol deviation: sekunimab 300 (5), sekunimab 150 (3), etanercept (3), placebo (0) Other: sekunimab 300 (0), sekunimab 150 (0), etanercept (5), placebo (2)
Interventions	Intervention A. Sekunimab 300 (n = 327), SC , 300 mg, weeks 0, 1, 2, 3, 4 and every 4 weeks, 12 weeks Control intervention B. Sekunimab 150 (n = 327), SC, 150 mg, weeks 0, 1, 2, 3, 4 and every 4 weeks, 12 weeks C. Etanercept 50 (n = 326), SC, 50 mg/week twice a week, 12 weeks D. Placebo (n = 326), SC, weeks 0, 1, 2, 3, 4 and every 4 weeks, 12 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 and a IGA score at 0 or 1 Secondary outcomes of the trial PASI 50, PASI 75, PASI 90, PASI 100 Response of 0 or 1 on the modified IGA at each study visit until week 52 Score of 0 or 1 on the DLQI at weeks 12 and 52
Notes	Funding source, quote (p 326): "funded by Novartis Pharmaceuticals" Declarations of interest (p 337): "Disclosure forms provided by the authors are available with the full text of this article at NEJM.org." Langley received personal fees from Eli Lilly, Leo, Novartis, Janssen, Amgen, AbbVie, Celgene, Merck, Pfizer."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (protocol and Appendix): "Randomization numbers were generated by the Interactive Response Technology (IRT) provider using a validated system, which automated the random assignment of subject numbers to randomisation numbers..." Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (protocol and Appendix): “Subjects, investigator staff, persons performing the assessments, and data analysts were blinded to the identity of the treatment from the time of randomisation until primary objective analyses" "Randomization numbers were generated by the Interactive Response Technology (IRT) provider" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (protocol and Appendix): “Subjects, investigator staff, persons performing the assessments, and data analysts were blinded to the identity of the treatment from the time of randomisation until primary objective analyses Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (protocol and Appendix): “Subjects, investigator staff, persons performing the assessments, and data analysts were blinded to the identity of the treatment from the time of randomisation until primary objective analyses Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote (p 329): "The analyses of the efficacy end points included all the patients who underwent randomisation according to the treatment assigned at randomisation... Missing values ... were conservatively imputed as nonresponses, regardless the reason of missing data" 1306 included/1306 analysed Comment: probably done
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01358578). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported.