P179 Head-to-head study of bimekizumab, an IL-17A/IL-17F inhibitor, and risankizumab, an IL-23 inhibitor, in patients with active psoriatic arthritis: study design and rationale of BE BOLD, a phase 3b, randomised, parallel-group study

Background/Aims Whilst there are multiple drug options for psoriatic arthritis (PsA), there is limited evidence on their comparative effectiveness and safety across clinical domains. Head-to-head studies are considered the gold standard for understanding the relative effectiveness and safety of drugs, allowing clinicians to make informed treatment decisions. Bimekizumab, a monoclonal antibody that selectively inhibits interleukin (IL)-17A/IL-17F, has demonstrated efficacy and tolerability in PsA. Risankizumab, an IL-23 inhibitor, has demonstrated efficacy in PsA. IL-23-responsive cells are a significant source of IL-17A/IL-17F. However, IL-17A/IL-17F, notably IL-17F, can be produced independently of IL-23. We hypothesise bimekizumab will be superior to risankizumab in joint efficacy, by blocking IL-17A/IL-17F derived from IL-23-dependent and -independent sources. To test this, we present the first head-to-head study comparing efficacy and safety of bimekizumab vs risankizumab in patients with active PsA. Here, we present the study design and rationale for the phase 3b BE BOLD study, including key clinical endpoints, and outline the hypothesis that bimekizumab will be superior to risankizumab in joint efficacy, by blocking IL-17A/IL-17F from both IL-23-dependent and -independent sources. Methods BE BOLD is a multicentre, phase 3b, randomised, double-blinded, active-controlled, parallel-group study. Patients with active PsA will be biologic disease-modifying antirheumatic drug-naïve or have inadequate response/intolerance to maximum one TNF inhibitor. Double-blinded period: 24 weeks. Approximately 550 patients will be randomised 1:1 to subcutaneous bimekizumab:risankizumab. Patients will be dosed according to approved bimekizumab and risankizumab labels for patients with PsA, based on psoriasis severity at baseline. Psoriasis severity thresholds: no/minimal psoriasis defined as body surface area (BSA) <3%; mild psoriasis as BSA ≥3% to < 10% or BSA ≥10% and either Investigator’s Global Assessment (IGA) score <3 or Psoriasis Area and Severity Index (PASI) score <12; moderate/severe psoriasis as BSA ≥10%, IGA score ≥3 and PASI score ≥12. Bimekizumab-randomised patients with no/mild psoriasis will receive subcutaneous bimekizumab 160 mg every 4 weeks (Q4W) to Week 24 with final dose of study drug at Week 20; patients with moderate/severe psoriasis will receive subcutaneous bimekizumab 320 mg Q4W to Week 16, then 320 mg Q8W. All risankizumab-randomised patients will receive subcutaneous risankizumab 150 mg at baseline, Week 4, then Week 16, regardless of baseline psoriasis severity. Results Primary endpoint (Week 16): American College of Rheumatology ≥50% improvement (ACR50; noninferiority/superiority vs risankizumab). Secondary endpoints: ACR50 at Week 4; Minimal Disease Activity response at Week 16; ACR50+PASI100 response at Week 16; safety outcomes (adverse events, including serious/leading to withdrawal). Conclusion BE BOLD is the first head-to-head study to evaluate efficacy and safety of bimekizumab, an IL-17A/IL-17F inhibitor, vs risankizumab, an IL-23 inhibitor, in patients with active PsA; testing for superiority of bimekizumab over risankizumab in joint disease, using the primary endpoint of ACR50 at Week 16. Disclosure J.F. Merola: Consultancies; AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Incyte, Janssen, LEO Pharma, MoonLake Immunotherapeutics, Novartis, Pfizer, Sanofi-Regeneron, Sun Pharma, UCB. I.B. McInnes: Consultancies; AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen, Eli Lilly and Company, MoonLake Immunotherapeutics, Novartis, UCB. Honoraria; AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, Causeway Therapeutics, Celgene, Evelo, Janssen, Eli Lilly and Company, MoonLake Immunotherapeutics, Novartis, UCB. Grants/research support; Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Janssen, Novartis, UCB. P.J. Mease: Consultancies; AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Cullinan, Eli Lilly and Company, GSK, Inmagene, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Takeda, UCB, Ventyx. Member of speakers’ bureau; AbbVie, Amgen, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, Sana, UCB. Y. Tanaka: Honoraria; AbbVie, Asahi-kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, Gilead, GSK, Pfizer, Taisho, UCB. Grants/research support; Boehringer-Ingelheim, Chugai, Taisho. A.B. Gottlieb: Honoraria; As an advisory board member and consultant for Amgen, AnaptysBio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, DICE Therapeutics, Eli Lilly and Company, Highlights Therapeutics, Janssen, Novartis, Sanofi, Teva, UCB, Xbiotech (stock options for RA). Grants/research support; Bristol Myers Squibb, Highlights Therapeutics, Janssen, UCB (all paid to Mount Sinai School of Medicine). A. Morita: Consultancies; AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly and Company, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB, Ushio. Grants/research support; AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly and Company, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharma, Taiho Pharmaceutical, Torii Pharmaceutical, UCB, Ushio. B. Ink: Shareholder/stock ownership; AbbVie, GSK, UCB. Other; Employee of UCB. A. Marten: Other; Employee of UCB. J. Coarse: Shareholder/stock ownership; UCB. Other; Employee of UCB. L. Gossec: Consultancies; AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Janssen, Moonlake, MSD, Novartis, Pfizer, Stada, UCB. Grants/research support; AbbVie, Biogen, Eli Lilly, Novartis, UCB.