IXORA‐P 2018.

Study characteristics
Methods	RCT, active/placebo‐controlled, double‐blind trial Date of study: August 2015 ‐ August 2017 Location: worldwide Phase 3
Participants	Randomised: 1227 participants Inclusion criteria Present with chronic plaque psoriasis for ≥ 6 months prior to enrolment ≥ 10% BSA of psoriasis at screening and at enrolment sPGA score of ≥ 3 and PASI score of ≥ 12 at screening and at enrolment Candidates for phototherapy and/or systemic therapy Participant must agree to use reliable method of birth control during the study; women must continue using birth control for ≥ 12 weeks after stopping treatment Exclusion criteria Predominant pattern of pustular, erythrodermic, or guttate forms of psoriasis History of drug‐induced psoriasis Cannot avoid excessive sun exposure or use of tanning booths for ≥ 4 weeks prior to enrolment and during the study Received systemic non‐biologic psoriasis therapy or phototherapy within the previous 4 weeks; or had topical psoriasis treatment within the previous 2 weeks prior to enrolment Concurrent or recent use of any biologic agent Have participated in any study with ixekizumab Received a live vaccination within 12 weeks prior to enrolment Serious disorder or illness other than psoriasis Ongoing or serious infection within the last 12 weeks or evidence of TB Major surgery within 8 weeks of baseline, or will require surgery during the study Breastfeeding or nursing (lactating) women Dropouts and withdrawals 148/1227 (12.1%) Ixekizumab 4‐week group (38), ixekizumab 2‐week group (72), ixekizumab 2/4‐week group (36) AEs: Ixekizumab 4‐week group (5), ixekizumab 2‐week group (17), ixekizumab 2/4‐week group (13) Protocol violation: Ixekizumab 4‐week group (1), ixekizumab 2‐week group (4), ixekizumab 2/4‐week group (1) Participant decision: ixekizumab 4‐week group (11), ixekizumab2‐week group (25) ixekizumab 2/4‐week group (11) Lost to follow‐up: Ixekizumab 4‐week group (9), ixekizumab 2‐week group (11), ixekizumab 2/4‐week group (7) Investigator decision: ixekizumab 4‐week group (2), ixekizumab2‐week group (4) ixekizumab 2/4‐week group (0) Absence of efficacy: Ixekizumab 4‐week group (4), ixekizumab 2‐week group (6), ixekizumab 2/4‐week group (5) death: Ixekizumab 4‐week group (2), ixekizumab 2‐week group (2), ixekizumab 2/4‐week group (2) Others: ixekizumab 4‐week group (3), ixekizumab2‐week group (5) ixekizumab 2/4‐week group (1)
Interventions	Intervention A. Ixekizumab (160 mg ixekizumab given as 2 SC injections at baseline and then 80 mg ixekizumab given as 1 SC injection every 2 weeks to week 52), n = 611 Control interventions B. Ixekizumab (160 mg ixekizumab given as 2 SC injections at baseline and then 80 mg ixekizumab given as 1 SC injection every 4 weeks to week 52), n = 310 C. Ixekizumab (160 mg ixekizumab given as 2 SC injections at baseline and then 80 mg ixekizumab given as 1 SC injection every 4 weeks to week 52, with a dose adjustment to Q2W until week 50 for patients meeting prespecified criteria to which investigators were blinded (Q4W/Q2W dose adjustment), n = 306
Outcomes	At week 52 Primary composite outcome PGA 0/1 Achieving 75% improvement in PASI 75 Secondary outcomes PASI 90 PASI 75 NAPSI Psoriasis Scalp Severity Index Palmoplantar PASI Itch Numeric Rating Scale DLQI
Notes	Funding Quote (p 1315): "This study was funded in full by Eli Lilly and Company, Indianapolis, IN, U.S.A" Conflict of interest Quote (p 1323): "R.G.L. has been a consultant and/or scientific adviser and/or investigator and/or scientific officer and/or speaker for AbbVie, Amgen, Celgene, Pfizer, Eli Lilly and Company, Novartis and Boehringer Ingelheim. K.P. has been a consultant and/or scientific adviser and/or investigator and/or scientific officer and/or speaker for Amgen, Anacor, AbbVie, Akros, Allergan, Astellas, AstraZeneca, Baxalta, Baxter, Bristol‐Myers Squibb, Boehringer Ingelheim, Can‐Fite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly and Company, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, Medimmune, Meiji Seika Pharma, Merck (MSD), Merck‐Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi/Genzyme, Takeda, UCB and Valeant. M.G. has been a consultant and/or scientific adviser and/or investigator and/or scientific officer and/or speaker for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galderma, Janssen, LEOPharma, Novartis, Pfizer, Akros, Dermira, UCB and Coherus. A.B. has been a consultant and/or scientific adviser and/or investigator and/or scientific officer and/or speaker for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Genentech/Roche, GlaxoSmithKline, Janssen, Eli Lilly and Company, LEO Pharma, Merck Sharp& Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, Sienna Pharmaceuticals, UCB, Valeant and Vidac. P.F. has been a consultant and/or scientific adviser and/or investigator and/or scientific officer and/or speaker for Abbot/AbbVie, Amgen, Bristol‐Myers Squibb, Boehringer Ingelheim, Celgene, Celtaxsys, Cutanea, Galderma, Genentech, GlaxoSmithKline/Stiefel, Janssen, LEO Pharma, Eli Lilly and Company, Novartis, Regeneron, Roche, Sanofi, Schering‐Plough/Merck, 3M/iNova/Valeant, UCB and Wyeth/Pfizer. C.M., L.Z., N.A. and P.P. are employees of/and or own stock in Eli Lilly and Company.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 1316): "This multicentre, randomized, double‐blinded, parallel group, phase III trial was conducted...Assignment to dosing regimens was determined by a computer‐generated random sequence using an interactive web response system (IWRS). Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (p 1316): "This multicentre, randomized, double‐blinded, parallel group, phase III trial was conducted...Assignment to dosing regimens was determined by a computer‐generated random sequence using an interactive web response system (IWRS). Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 1316): "This multicentre, randomized, double‐blinded, parallel group, phase III trial was conducted...... To maintain investigator blinding, site personnel entered an sPGA score into the IWRS every 4 weeks, beginning at week 0 through week 48." Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 1316): "This multicentre, randomized, double‐blinded, parallel group, phase III trial was conducted...... To maintain investigator blinding, site personnel entered an sPGA score into the IWRS every 4 weeks, beginning at week 0 through week 48." Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote (p 1317): "Missing data were imputed as nonresponse (NRI). The multiple imputation (MI) method was also used to impute missing values as a sensitivity analysis..." Included population 1227, table 2 1227 Comment: done
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT02513550) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported Results are posted on ClinicalTrials.gov