NCT02690701.

Study characteristics
Methods	RCT, placebo‐controlled, double‐blind study Date of study: February 2016 ‐ February 2018 Location: USA (12 centres) Phase 4
Participants	Randomised: 91 participants Inclusion criteria Men and women ≥ 18 years with moderate‐severe plaque psoriasis (≥ 6 months prior to randomisation), with ≥ 10% BSA involvement, PASI ≥ 12, and IGA mod 2011 score ≥ 3 (based on a scale of 0 to 4) Eligible for systemic therapy Exclusion criteria Forms of psoriasis other than chronic plaque psoriasis Previous exposure to IL‐17A or IL‐17 receptor targeting agents Other active or ongoing disease that may interfere with evaluation of psoriasis or places the participant at unacceptable risk Used cholesterol‐lowering medications (unless the use of cholesterol‐lowering medications involved a dose that was stable ≥ 90 days prior to randomisation and remained stable during the study) Notable current cardiovascular or cerebrovascular disease Significant medical problems (uncontrolled hypertension with measured systolic ≥ 180 mmHg and/or diastolic ≥ 95 mm Hg, congestive heart failure) Serum creatinine level of > 2.0 mg/dL, a fasting blood glucose ≥150 mg/dL, or a total white blood cell (WBC) count < 2500/μl, thrombocytes < 100,000/μl, neutrophils < 1500/μl, or haemoglobin < 8.5 g/dL Baseline characteristics N = 91, mean age of 47.5 years and 67% men Dropouts and withdrawals 5/91 (5.5%): Secukinumab group (2), Placebo group (3) AEs: Secukinumab group (2), Placebo group (2) Participant/guardian decision: Secukinumab group (0), Placebo group (1)
Interventions	Intervention A. Secukinumab 300 (300 mg once weekly at baseline, weeks 1, 2, 3 and 4 followed by monthly dosing starting at week 8 through week 48 inclusive), n = 46 Control intervention B. Placebo, n = 45
Outcomes	At week 12 Primary outcome Aortic vascular inflammation as measured by FDG‐PET/CT Secondary outcomes Cardiometabolic biomarkers PASI 75 PASI 90 PASI 100 IGA 0/1 DLQI
Notes	Funding "This study is funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ." Conflict of interest "Dr Gelfand served as a consultant for BMS, Boehringer Ingelheim, Janssen Biologics, Novartis Corp, UCB (DSMB), Sanofi, and Pfizer, receiving honoraria; and receives research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Boehringer Ingelheim, Janssen, Novartis, Celgene, Ortho Dermatologics, and Pfizer; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly, Ortho Dermatologics, and Novartis. Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology. Dr Duffin has received research grants from AbbVie, Amgen, Bristol‐Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Sienna Biopharmaceuticals, Stiefel Laboratories, and UCB; and has received consulting fees from AbbVie, Amgen, Bristol‐Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Ortho Dermatologic, Pfizer, Sienna Biopharmaceuticals, Stiefel Laboratories, and UCB; and is on the speaker's bureau for Novartis. Dr Armstrong has served as investigator, advisor, and/or consultant to Leo, AbbVie, UCB, Janssen, Novartis, Eli Lilly, Sun, Dermavant, BMS, Regeneron Pharmaceuticals, Inc., Sanofi U.S., Dermira, Modmed, and Ortho Dermatologics, Inc. Dr Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer Ingelheim, Bristol‐ Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly, FLX Bio, Forte, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Meiji, Merck Sharp & Dohme, Novartis, Ortho, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, SiennaPharmaceuticals, Sun Pharma, UCB Pharma, and Vidac and as a paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. Dr Trying has conducted studies sponsored by the producer of secukinumab. Dr Menter has received compensation from or served as an investigator, consultant, advisory board member, or speaker for Abbott Labs, AbbVie, Allergan, Amgen, Anacor, Boehringer Ingelheim, Celgene, Dermira, Eli Lilly, Galderma, Janssen, Leo, Merck & Co, Neothetics, Novartis, Pfizer, Regeneron, Sienna, Symbio/Maruho, UCB, Vitae, and Xenoport. Dr Gottlieb is currently serving as consultant, advisory board member, speaker for Janssen, Celgene, Bristol Myers Squibb, Beiersdorf, Abbvie, UCB, Novartis, Incyte, Lilly, Reddy Labs, Valeant, Dermira, Allergan, Sun Pharmaceutical Industries, Xbiotech, Leo, Avotres Therapeutics. Research/Educational Grants: Janssen, Incyte, UCB, Novartis, Lilly Xbiotech, Boeringer Ingelheim. Dr Lockshin reports personal fees from Lilly, Novartis, Janssen, and Abbott; has served as a speaker for Novartis, Eli Lilly, and Abbvie; conducted research for Celgene, Abbvie, Novartis, Eli Lilly, and Strata, and served as a consultant for Novartis, Lilly, AstraZeneca, Abbive. Dr. Simpson reports grants from Eli Lilly, Kyowa Hakko Kirin, Leo Pharmaceutical, Merck, Pfizer, and Regeneron, and personal fees from Menlo Therapeutics, Valeant, Novartis, Eli Lilly, Galderma, Dermira, Sanofi Genzyme, Pfizer, Regeneron, and Leo Pharmaceuticals. Dr Shin, Dr Ahlman, Dr Playford, Dr Joshi, Dr Dey, Dr Werner and Dr Alavi have nothing to disclose.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "This was a randomized, double‐blinded, placebo‐controlled, parallel‐group, multicenter study in adult patients (≥18 years of age) with moderate‐to‐severe chronic plaque psoriasis....Eligible patients were randomized via Interactive Response Technology in a 1:1 ratio to either secukinumab 300 mg or placebo."
Allocation concealment (selection bias)	Low risk	Quote: "The Investigator or his/her delegate will contact the IRT after confirming that the subject fulfills all the inclusion/exclusion criteria. The IRT will assign a randomization number to the subject, which will be used to link the subject to a treatment group and will specify a unique medication number for the first box of study treatment to be dispensed to the subject. The randomization number will not be communicated to the caller. The identity of secukinumab and placebo prefilled syringes (PFS) will be concealed by identical packaging, labeling, schedule of administration, and appearance." Comment: adequate procedure to guarentee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote:"Patients, investigators/site staff, persons performing assessments, and Novartis study personnel remained blinded to individual treatment assignment from time of randomization until the final database lock at Week 52." Comment: adequate procedure to guarentee blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote:"Patients, investigators/site staff, persons performing assessments, and Novartis study personnel remained blinded to individual treatment assignment from time of randomization until the final database lock at Week 52." Comment: adequate procedure to guarentee blinding of assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dealing with missing data: Quote:"The primary analysis was based on the full analysis set.For the primary efficacy variable, data for patients with missing post‐baseline value were not imputed, and patients were included in the analysis if they had both baseline and post‐baseline assessments. The primary analysis was based on the full analysis set. Changes from baseline in each cardiometabolic biomarker were analyzed at each time point using the same ANCOVA model as for the primary efficacy variable; missing data were imputed using the last‐observation‐carried‐forward method." Randomised 91; analysed 91
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT02690701) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported. Results are posted on ClinicalTrials.gov