Background: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa., Methods: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed., Findings: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed., Interpretation: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa., Funding: UCB Pharma., Competing Interests: Declaration of interests ABK reports grants paid to the institution from AbbVie, Admirx, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly and Company, Incyte, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Prometheus, Sonoma Bio, and UCB Pharma; consulting fees from AbbVie, Alumis, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB Pharma, Union, and Ventyx; and serves on the board of directors of Almirall. GBEJ reports honoraria for participation on advisory boards from AbbVie, Boehringer Ingelheim, Chemocentryx, Incyte, Janssen-Cilag, LEO Pharma, Novartis, and UCB Pharma; and acted as an investigator for AbbVie, CJSL, InflaRx, Janssen-Cilag, LEO Pharma, Novartis, Regeneron, Sanofi, and UCB Pharma. CJS acted as an investigator for AbbVie, Chemocentryx, GSK, Incyte, InflaRx, Novartis, and UCB Pharma; reports consultancy fees from AbbVie, Alumis, InflaRx, Incyte, Logical Images, Sonoma Biotherapeutics, and UCB Pharma; and acted as a speaker for AbbVie and Novartis. JSK reports personal fees from AbbVie, ChemoCentryx, CJSL Behring, DermTech, Incyte, Insmed, Janssen, MoonLake, Novartis, and UCB Pharma; personal fees and grants from Incyte; is a co-copyright holder of HiSQOL; has been a consultant for and received honoraria from AbbVie, Alumis, DermTech, Incyte, Insmed, Janssen, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and has been a speaker for AbbVie, Janssen, Novartis, and UCB Pharma. EP has been a consultant, advisory board member, speaker for, and received honoraria from Almirall, Janssen-Cilag, GSK, MoonLake Immunotherapeutics, Novartis, and UCB Pharma; and his department received investigator-initiated grant support from AbbVie, Celgene, CHDR, Citryll, Kymera, Janssen-Cilag, and UCB Pharma. JRI receives a stipend as Editor‑in‑Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate; has been a consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Citryll, MoonLake Immunotherapeutics, Novartis, UCB Pharma, and Union Therapeutics, and has served on advisory boards for Insmed, Kymera Therapeutics, and Viela Bio; is a co‑copyright holder of the Hidradenitis Suppurativa Quality of Life score (HiSQOL) and hidradenitis suppurativa-Investigator Global Assessment; and his department receives income from copyright of the Dermatology Life Quality Instrument and related instruments. AG has been a consultant and receives honoraria from AbbVie, Aclaris Therapeutics, AnaptysBio, Aristea Therapeutics, Bristol Myers Squibb, Boehringer Ingelheim, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB Pharma, Union Therapeutics, Ventyx Biosciences, and Viela Biosciences; has received research grants from AbbVie, C3, National Psoriasis Foundation, and UCB Pharma; and is a co-copyright holder of HiSQOL and hidradenitis suppurativa-IGA. ABG reports honoraria as an advisory board member and consultant for Amgen, Almirall, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapeutics, Eli Lilly and Company, Janssen, Novartis, Sanofi, UCB Pharma, and Xbiotech; and research or educational grants from AnaptysBio, Bristol Myers Squibb, MoonLake Immunotherapeutics, Novartis, and UCB Pharma (all paid to Mount Sinai School of Medicine). JCJS has acted as a consultant and advisory board member of AbbVie, LEO Pharma, Novartis, Pierre Fabre, Sanofi Genzyme, and Trevi Therapeutics; acted as a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Novartis, Pfizer, Pierre-Fabre, Sanofi, and UCB Pharma; and has acted as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRX, Janssen, Kliniksa, Kymab Limited, Menlo Therapeutics, Merck, Novartis, Pfizer, Regereron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. FGB reports honoraria for participation in advisory boards, in clinical trials, and as a speaker from AbbVie, AbbVie Deutschland, Boehringer Ingelheim, Celltrion, Dr. Wolff, Incyte, Janssen, Mölnlycke, MoonLake Immunotherapeutics, Novartis, and UCB Pharma. EJG-B reports honoraria from Abbott Products Operations, bioMérieux, Brahms, GSK, InflaRX, Sobi and XBiotech; independent educational grants from Abbott Products Operations, AxisShield, bioMérieux, InflaRx, Johnson & Johnson, MSD, Novartis, Sobi, and XBiotech; and funding from the Horizon2020 Marie Skłodowska-Curie International Training Network the European Sepsis Academy (granted to the National and Kapodistrian University of Athens), the Horizon 2020 European Grants ImmunoSep and RISCinCOVID (granted to the Hellenic Institute for the Study of Sepsis) and the Horizon Health grant EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis). HF reports honoraria or fees for serving on advisory boards, as a speaker, and as a consultant; and grants as an investigator from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly and Company, Janssen, Japan Blood Products Organization, JMEC, Kaken Pharmaceutical, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nihon Pharmaceutical, Novartis, Otsuka Pharmaceutical, Sanofi, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB Pharma, and Ushio. RR, PJ, PD, EM, and LP are employees and shareholders of UCB Pharma. CM is a former employee and shareholder of UCB Pharma. MB is an employee of UCB Pharma. CCZ reports grants paid to the institution from AstraZeneca, Boehringer Ingelheim, GSK, InflaRx, Novartis, Relaxera, and UCB Pharma for participation as a clinical and research investigator; consultant honoraria from AccureAcne, Almirall, Boehringer Ingelheim, Incyte, InflaRx, Janssen, L'Oréal, Luvos, NAOS-BIODERMA, Novartis, PPM, Sanofi, UCB Pharma, and Viatris; lecture fees from Almirall, Biogen, Novartis, Sobi, and UCB Pharma; and is the president of the European Hidradenitis Suppurativa Foundation, coordinator of the ALLOCATE Skin group of the European Reference Network for rare skin diseases, and chair of the Acne, Rosacea and Hidradenitis Suppurativa Task Force group of the European Academy of Dermatology and Venereology (EADV); is the editor of the EADV News; and co-copyright holder of the International Hidradenitis Suppurativa Severity Score System on behalf of the European Hidradenitis Supurativa Foundation., (Copyright © 2024 Elsevier Ltd. 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