POS0215 LONG-TERM SAFETY AND EFFICACY OF BIMEKIZUMAB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: 5-YEAR RESULTS FROM A PHASE 2B STUDY AND ITS OPEN-LABEL EXTENSION
Authors: A. Deodhar, V. Navarro-Compán, D. Poddubnyy, L. S. Gensler, S. Ramiro, T. Tomita, H. Marzo-Ortega, C. Fleurinck, T. Vaux, U. Massow, D. Van der Heijde, X. Baraliakos
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Bimekizumab (BKZ), a monoclonal IgG1 antibody, selectively inhibits interleukin (IL)-17F in addition to IL17A. BKZ has demonstrated clinical efficacy and safety up to 3 years (yrs) in patients (pts) with active ankylosing spondylitis ([AS] i.e., radiographic axial spondyloarthritis)[1] in the phase 2b study BE AGILE and its open-label extension (OLE).[2] <h3>Objectives:</h3> To report the 5-yr efficacy and safety results of BKZ in BE AGILE and its OLE. <h3>Methods:</h3> BE AGILE (NCT02963506) consisted of a 12-week (wk) double-blind, placebo-controlled period, then a dose-blind (DB) period to Wk 48 where pts received BKZ 160 or 320 mg every 4 wks (Q4W).[2] Pts completing Wk 48 were eligible to enter the OLE (NCT03355573) where all received BKZ 160 mg Q4W to Wk 256. Treatment-emergent adverse events (TEAEs; MedDRA v19.0) are reported for BKZ exposure from Wk 0–256. Efficacy is reported from Wk 0–256 for pts enrolled in BE AGILE entering the DB period (DB set [DBS]) and Wk 48–256 for pts enrolled in the OLE with ≥1 efficacy measurement at OLE entry (OLE full analysis set [FAS]). Analyses used non-responder imputation (NRI), observed case methodology or multiple imputation (MI). <h3>Results:</h3> 296/303 (97.7%) pts randomised in BE AGILE entered the DB period; 265/303 (87.5%) completed to Wk 48. Of 255/303 (84.2%) pts who entered the OLE at Wk 48 and received ≥1 BKZ dose, 202/255 (79.2%) completed to Wk 256. From Wk 0–256, exposure adjusted incidence rates (EAIRs) per 100 pt-yrs were 134.6 for any TEAE and 5.2 for serious TEAEs (Table 1). EAIR of Candida infections over 256 wks (2.6) was lower than in Wk 0–48 (7.5).[2] All Candida infections were mild or moderate; 1 oral candidiasis event led to discontinuation. No systemic fungal infections were reported. Over 256 wks, EAIRs of serious infections and infestations (1.4) and injection site reactions (0.2) remained low. EAIRs of IBD (0.8) and uveitis (0.7) were also low. At OLE entry, around half of the DBS (n=296) achieved Assessment of SpondyloArthritis international Society 40% response (ASAS40; 51.7%) and AS Disease Activity Score (ASDAS) &lt;2.1 (49.3%); 49.7% and 41.6% achieved these endpoints at Wk 256, respectively (NRI; Figure 1). Similar results were seen in the OLE FAS (n=249) for ASAS40 (NRI; Wk 48: 59.8%; Wk 256: 59.0%) and ASDAS &lt;2.1 (MI; 57.3%; 66.0%). Mean reductions from baseline to Wk 48 in ASDAS (3.9 to 2.1) and Bath AS Disease Activity Index (BASDAI [6.5 to 3.0]) in the DBS were sustained or decreased to 2.1 and 2.5, respectively, at Wk 256 (MI); responses in the OLE FAS from Wk 48 to Wk 256 were similar (MI; ASDAS: 2.0 to 1.9; BASDAI: 2.8 to 2.4). Mean Bath AS Function Index (BASFI) and AS quality of life (ASQoL) improvements from baseline to Wk 48 were sustained to Wk 256 in the DBS (MI; Figure 1), and from Wk 48 to Wk 256 in the OLE FAS (MI; BASFI: 3.0 to 2.6; ASQoL: 3.3 to 2.6). <h3>Conclusion:</h3> The long-term safety profile of BKZ in pts with AS was consistent with previous observations, with no new safety signals identified after 5 yrs of exposure. Clinical efficacy, including improvements in signs and symptoms, disease activity, physical function and health-related quality of life, was maintained up to 5 yrs of BKZ treatment. To our knowledge, this is the first report of NRI ASAS40 data up to 5 yrs in pts with AS exposed to novel treatments. <h3>REFERENCES:</h3> [1] Boel A. Ann Rheum Dis 2019;78:1545–9. [2] Baraliakos X. Arthritis Rheumatol 2022;74:1943–58. <h3>Acknowledgements:</h3> Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma. <h3>Disclosure of Interests:</h3> Atul Deodhar Speakers bureau for Janssen, Novartis and Pfizer, Consultant for AbbVie, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma, Victoria Navarro-Compán Speakers bureau for AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant for AbbVie, Eli Lilly, Galapagos, Moonlake, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from AbbVie and Novartis, Denis Poddubnyy Speaker for AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer and UCB Pharma, Consultant for AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB Pharma, Grant/research support from AbbVie, Eli Lilly, MSD, Novartis and Pfizer, Lianne S Gensler Consulting fees from Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma, Grants from Novartis and UCB Pharma paid to institution, Sofia Ramiro Consulting fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi and UCB Pharma, Grants from AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma, Tetsuya Tomita Speaker fees from AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer, Consulting fees from AbbVie, Eli Lilly, Gilead, Novartis and Pfizer, Helena Marzo-Ortega Speaking honoraria and/or consulting fees from AbbVie, Amgen, Biogen, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, Takeda and UCB Pharma, Research grants from Janssen, Novartis, Pfizer and UCB Pharma, Carmen Fleurinck Shareholder of UCB Pharma, Employee of UCB Pharma, Tom Vaux Employee of UCB Pharma, Ute Massow Employee of UCB Pharma, Désirée van der Heijde Director of Imaging Rheumatology BV, Consulting fees from AbbVie, Bayer, BMS, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer, Takeda and UCB Pharma, Xenofon Baraliakos Paid instructor for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma, Speakers bureau from AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma, Consultant of AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma, Grant/research support from Novartis and UCB Pharma.