Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors., Methods: BE COMPLETE was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted across 92 sites (including hospitals, clinics, and research centres) in 11 countries (Australia, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Poland, Russia, the UK, and the USA). Eligible patients were aged 18 years or older with adult-onset psoriatic arthritis (meeting the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening) with a history of inadequate response or intolerance to treatment with one or two TNFα inhibitors for either psoriatic arthritis or psoriasis. We stratified patients with active psoriatic arthritis by region and previous TNFα inhibitor use. Patients were randomly assigned (2:1) to receive subcutaneous bimekizumab 160 mg every 4 weeks or placebo by an interactive-voice and web-response system on the basis of a predetermined randomisation schedule. The primary endpoint was the proportion of patients with 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses were done in the randomised population. The safety analysis set comprised patients who received one or more doses of study treatment. This trial was registered at ClinicalTrials.gov, NCT03896581, and is completed., Findings: Between March 28, 2019, and Feb 14, 2022, 556 patients were screened and 400 patients were randomly assigned to bimekizumab 160 mg every 4 weeks (n=267) or placebo (n=133). The primary and all hierarchical secondary endpoints were met at week 16. 116 (43%) of 267 patients receiving bimekizumab reached ACR50, compared with nine (7%) of 133 patients receiving placebo (adjusted odds ratio [OR] 11·1 [95% CI 5·4-23·0], p<0·0001). 121 (69%) of 176 patients with psoriasis affecting at least 3% body surface area at baseline who received bimekizumab reached 90% or greater improvement in the Psoriasis Area and Severity Index (PASI90), compared with six (7%) of 88 patients who received placebo (adjusted OR 30·2 [12·4-73·9], p<0·0001). Treatment-emergent adverse events up to week 16 were reported in 108 (40%) of 267 patients receiving bimekizumab and 44 (33%) of 132 patients receiving placebo. There were no new safety signals and no deaths., Interpretation: Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFα inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors., Funding: UCB Pharma., Competing Interests: Declaration of interests JFM reports work as a consultant or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma. RL reports consultancy fees from Abbott, Ablynx, Amgen, AstraZeneca, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth; research grants from Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth; and speaker's bureau fees from Abbott, Amgen, BMS, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, and Wyeth. IBM reports consulting fees and honoraria from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, and UCB Pharma; and research support from BMS, Boehringer Ingelheim, Celgene, Janssen, and UCB Pharma. PJM reports research grants from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, and UCB Pharma; and speakers' bureau fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma. CTR reports research for AbbVie, Amgen, and UCB Pharma; and consultancy for Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. YT reports speaking fees or honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe, and Pfizer; and research grants from Asahi-Kasei, AbbVie, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, and Takeda. AA reports honoraria or research grants from AbbVie, Amgen, BMS, Boehringer Ingelheim, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi-Tanabe, Pfizer, Sun Pharma, Taiho Pharma, Torii Pharmaceutical, and UCB Pharma. FB reports work as a consultant, speaker, or investigator for AbbVie, Affibody, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, GSK, Janssen, MSD, MoonLake, Novartis, Pfizer, Roche, Sandoz, and Sanofi. DDG received grants from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma; and consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma. LG reports non-financial support from UCB Pharma during the conduct of the study; grants from Amgen, Eli Lilly, Galapagos, Pfizer, Sandoz, and UCB Pharma; personal fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Sandoz, and UCB Pharma; and non-financial support from AbbVie, Janssen, Novartis, Pfizer, and UCB Pharma outside the submitted work. ABG reports honoraria as an advisory board member, non-promotional speaker, or consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech (stock options); and research or educational grants from AnaptysBio, BMS, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, and UCB Pharma (all funds go to the Icahn School of Medicine at Mount Sinai). DT reports honoraria for participation on advisory boards as a speaker and for consultancy from AbbVie, Almirall, Amgen, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Samsung, Sanofi Genzyme, and UCB Pharma; and research grants from LEO Pharma and Novartis. RBW reports consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, GSK, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB Pharma; research grants to his institution from AbbVie, Almirall, Janssen, LEO Pharma, Novartis, and UCB Pharma; and honoraria from Astellas, DiCE, GSK, and Union. BI is an employee of UCB Pharma, and stockholder of AbbVie, GSK, and UCB Pharma. DA, RB, VS, and JC are all employees and stockholders of UCB Pharma. LCC reports grants and research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma; paid consultancy for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer, and UCB Pharma; and speaker fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, and UCB Pharma., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)