POS1022 BIMEKIZUMAB SAFETY AND EFFICACY IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM A PHASE 2b OPEN-LABEL EXTENSION STUDY
Authors: L. C. Coates, R. B. Warren, C. T. Ritchlin, L. Gossec, J. F. Merola, D. Assudani, J. Coarse, J. Eells, B. Ink, I. Mcinnes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Bimekizumab (BKZ), a monoclonal antibody inhibitor of interleukin (IL)-17A and IL-17F, demonstrated clinical improvements in joint and skin outcomes up to 108 weeks (wks) in patients (pts) with active psoriatic arthritis (PsA). 1,2 Objectives: To report up to 3-year safety and efficacy of BKZ in pts with active PsA from a 48-week phase 2b dose-ranging study (BE ACTIVE; NCT02969525 ) and its open-label extension (OLE; NCT03347110 ). Methods: BE ACTIVE and OLE study design has been described previously. 1 All OLE pts received BKZ 160 mg Q4W, irrespective of prior dosing regimen. Treatment-emergent adverse events (TEAEs) are reported for the safety set (SS; pts who received ≥1 dose BKZ in the dose-ranging study). Data are presented from dose-ranging study baseline (BL) to Wk 152. Efficacy outcomes are reported for the full analysis set (FAS): ACR50, minimal or very low disease activity (MDA/VLDA), Psoriasis Area and Severity Index (PASI) 90/100, body surface area affected by psoriasis (BSA) 0% and dactylitis/enthesitis resolution. Results: Over 152 wks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) was 126.4 for all TEAEs, 4.1 for serious TEAEs, 0.7 for serious infections and 4.6 for Candida infections (Table 1). One event was adjudicated by an independent committee as inflammatory bowel disease (microscopic colitis). All Candida infections were localised, mild/moderate, and resolved with appropriate anti-fungal therapy. Overall, the proportions of patients with ACR50 response were sustained through Wk 152 (52.9%, non-responder imputation [NRI]; Figure 1). Response rates were also sustained through Wk 152 for MDA (51.5%), VLDA (30.1%), PASI90 (64.2%), PASI100 (57.7%) and resolution of dactylitis (71.2%) and enthesitis (62.6%) (NRI; Table 1). Table 1. Safety and efficacy outcomes up to 3 years Safety (SS ) n (%) [EAIR/100 PY] BKZ 160 mg [a] (n=126 ) BKZ 320 mg [b] (n=78 ) Total (N=206 ) Any TEAE 114 (90.5) [136.1] 70 (89.7) [113.3] 184 (89.3) [126.4] Serious TEAEs 17 (13.5) [5.2] 5 (6.4) [2.3] 22 (10.7) [4.1] Key TEAEs of special monitoring Serious infections 3 (2.4) [0.9] 1 (1.3) [0.5] 4 (1.9) [0.7] Candida infections 15 (11.9) [4.7] 9 (11.5) [4.4] 24 (11.7) [4.6] Inflammatory bowel disease [c] 1 (0.8) [0.3] 0 1 (0.5) [0.2] Malignancies [d] 1 (0.8) [0.3] 0 1 (0.5) [0.2] Injection site reactions 0 3 (3.8) [1.4] 3 (1.5) [0.5] Suicidal ideation 1 (0.8) [0.3] 0 1 (0.5) [0.2] Liver function analyses 13 (10.3) [4.1] 11 (14.1) [5.3] 24 (11.7) [4.6] Study discontinuation due to TEAEs 12 (9.5) [3.5] 4 (5.1) [1.8] 16 (7.8) [2.8] Efficacy (FAS ) n (%) BKZ 160 mg [a] (n=124 ) BKZ 320 mg [b] (n=82 ) Total (N=206 ) OC NRI, % OC NRI, % OC NRI, % MDA, Wk 152 64/95 (67.4) 51.6 42/62 (67.7) 51.2 106/157 (67.5) 51.5 VLDA, Wk 152 41/95 (43.2) 33.1 21/62 (33.9) 25.6 62/157 (39.5) 30.1 PASI90 [e] Wk 152 51/61 (83.6) 64.6 37/46 (80.4) 63.8 88/107 (82.2) 64.2 PASI100 [e] Wk 152 47/61 (77.0) 59.5 32/46 (69.6) 55.2 79/107 (73.8) 57.7 BSA 0% [e] Wk 48 48/72 (66.7) 60.8 38/55 (69.1) 65.5 86/127 (67.7) 62.8 Wk 152 46/61 (75.4) 58.2 31/45 (68.9) 53.4 77/106 (72.6) 56.2 Dactylitis [f]/Enthesitis [g] resolution, Wk 48 – 70.6/56.9 – 84.0/57.1 – 76.3/57.0 Wk 152 – 67.6/63.1 – 76.0/61.9 – 71.2/62.6 No anaphylactic reactions or major adverse cardiac events were reported. [a] Includes pts within the indicated analysis set originally assigned to all arms who were subsequently re-randomized to 160 mg, or [b] 320 mg, after double-blind period; [c] Microscopic colitis; [d] Malignant melanoma in situ; [e] Pts with BL BSA ≥3%, NRI: n=79, 58, 137 respectively; [f] Pts with BL LDI &gt;0, NRI: n=34, 25, 59 respectively; [g] Pts with BL MASES &gt;0, NRI: n=65, 42, 107 respectively. LDI: Leeds Dactylitis Index; MASES: Maastricht AS Enthesitis Score; OC: observed case. Conclusion: The safety profile of BKZ in pts with PsA reflects previous observations 1,2 for up to 3 years. High threshold disease control was achieved by &gt;50% of BKZ-treated pts up to 3 years, reflected in long-term improvements in joint and skin outcomes. References: [1]Ritchlin CT. Lancet 2020;395:427–40; [2]McInnes I. Ann Rheum Dis 2020;79:1153–4. Acknowledgements: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interests: Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, GSK, Janssen, Lilly, Medac, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Domain, Gilead, Janssen, Lilly, Grant/research support from: AbbVie, Amgen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Arena, Avillion, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi, UCB Pharma, Grant/research support from: AbbVie, Almirall, Amgen, Janssen, LEO Pharma, Novartis, UCB Pharma, Christopher T. Ritchlin Consultant of: Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB Pharma, Laure Gossec Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Samsung, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer, Samsung, Sanofi, UCB Pharma, Grant/research support from: Eli Lilly, Pfizer, Sandoz, Joseph F. Merola Consultant of: AbbVie, Amgen, Bayer, Biogen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Sanofi-Regeneron, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Amgen, Bayer, Biogen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Sanofi-Regeneron, Pfizer, UCB Pharma, Principal investigator for Dermavant, LEO Pharma, UCB Pharma, Deepak Assudani Employee of: UCB Pharma, Jason Coarse Employee of: UCB Pharma, Jason Eells Shareholder of: UCB Pharma, Employee of: UCB Pharma, Barbara Ink Shareholder of: GSK, UCB Pharma, Employee of: UCB Pharma, Iain McInnes Consultant of: AbbVie, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Novartis, UCB Pharma, Grant/research support from: BMS, Boehringer Ingelheim, Celgene, Janssen, UCB Pharma.