Pos1104 bimekizumab maintained stringent clinical responses through week 52 in patients with axial spondyloarthritis: results from the phase 3 studies be mobile 1 and be mobile 2

Background Axial spondyloarthritis (axSpA) is a chronic rheumatic disease which requires optimal management and disease control. Assessment of SpondyloArthritis international Society ≥40% improvement (ASAS40) is a stringent efficacy outcome in clinical trials, while in clinical practice the focus is on the achievement of sustained remission or low disease activity (LDA) according to Ankylosing Spondylitis Disease Activity Score (ASDAS). Patients (pts) can experience loss of response in the long term and maintenance of response is an internationally recommended treatment target.[1] Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL‑17A. BKZ has demonstrated consistent and sustained clinical efficacy to Week (Wk) 52 in pts across the full spectrum of axSpA in the phase 3 studies BE MOBILE 1 and 2.[2] Objectives To report the maintenance of stringent clinical responses through one year of treatment with BKZ in pts with non‑radiographic axSpA (nr-axSpA) and radiographic-axSpA (r‑axSpA, i.e., ankylosing spondylitis)[3] in phase 3 studies. Methods In BE MOBILE 1 (NCT03928704; nr-axSpA; pts met ASAS criteria for axSpA) and BE MOBILE 2 (NCT03928743; r‑axSpA; pts fulfilled ASAS and modified New York criteria for r-axSpA), pts were randomised to receive subcutaneous BKZ 160 mg every 4 wks (Q4W) or placebo (PBO) to Wk 16. From Wks 16−52, all pts received BKZ 160 mg Q4W.[4,5] ASAS40 and ASDAS <2.1 (LDA) or <1.3 (inactive disease [ID]) responses to Wk 52 were assessed among BKZ‑randomised pts who responded at Wk 16. Missing ASAS40 data were imputed using non-responder imputation (NRI), and multiple imputation (MI) was used for missing ASDAS data. MI was based on Markov Chain Monte Carlo (for intermittent missing data) followed by monotone regression (for monotone missing data). Observed case (OC) data are also reported. Wk 16 and Wk 52 responder rates for all BKZ-randomised pts are included for context (NRI or MI). The number of treatment-emergent adverse events (TEAEs) to Wk 52 are reported for pts who received ≥1 dose of BKZ, including pts who switched from PBO to BKZ at Wk 16. Results A total of 128 and 221 pts were randomised to BKZ 160 mg Q4W in BE MOBILE 1 and 2, respectively. At Wk 16, 47.7% and 44.8% of these pts achieved the primary endpoint, ASAS40, and this increased to 60.9% and 58.4% at Wk 52 (NRI, Figure 1). Of pts that achieved ASAS40 at Wk 16, 82.0% and 83.8% maintained this response at Wk 52 (NRI, Figure 1). ASDAS LDA was achieved by 46.1% and 44.8% of BKZ-randomised pts at Wk 16 of BE MOBILE 1 and 2, respectively; this increased to 61.6% and 57.1% at Wk 52 (MI, Figure 1). Of pts that achieved ASDAS LDA at Wk 16, 88.9% and 88.4% maintained this response at Wk 52 (MI, Figure 1). At Wk 16 of BE MOBILE 1 and 2, ASDAS ID was achieved by 18.8% and 16.4% of BKZ‑randomised pts, respectively; and this increased to 25.2% and 23.4% at Wk 52 (MI). Among Wk 16 ASDAS ID responders, ASDAS ID was maintained by 79.2% and 75.1% at Wk 24, 85.3% and 71.7% at Wk 36, and 88.0% and 58.7% at Wk 52 (MI). To Wk 52 of BE MOBILE 1 and 2, 183/244 (75.0%) and 249/330 (75.5%) pts reported ≥1 TEAE whilst receiving BKZ, respectively; 9 (3.7%) and 20 (6.1%) reported serious TEAEs. Conclusion Dual inhibition of IL-17F and IL-17A with BKZ provided robust maintenance of stringent clinical responses from Wk 16 to Wk 52 across the full axSpA disease spectrum. This is consistent with previously reported observations of BKZ treatment over three years in pts with r-axSpA in the phase 2b study BE AGILE and its open-label extension.[6] References [1] Smolen J. Ann Rheum Dis 2018;77:3–17; [2] Baraliakos X. Arthritis Rheumatol 2022;74 (suppl 9); [3] Boel A. Ann Rheum Dis 2019;78:1545–9; [4] Deodhar A. Ann Rheum Dis 2022;81:772–3; [5] van der Heijde D. Ann Rheum Dis 2022;81:12–3; [6] Navarro-Compán V. Presented at EULAR 2022, POS0938. Acknowledgements This study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma. Disclosure of Interests Fabian Proft Speakers bureau: AbbVie, Amgen, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, BMS, Celgene, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB Pharma, Grant/research support from: Eli Lilly, Novartis and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, Employee of: Director of Imaging Rheumatology BV, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Joerg Ermann Consultant of: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB Pharma, Grant/research support from: Abbvie, Boehringer Ingelheim, Novartis and Pfizer, Carmen Fleurinck Employee of: UCB Pharma, Ute Massow Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Vanessa Taieb Employee of: UCB Pharma, Astrid van Tubergen Speakers bureau: Pfizer, Consultant of: Novartis, Pfizer and UCB Pharma, Grant/research support from: MSD, Novartis, Pfizer and UCB Pharma, Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Galapagos, Moonlake, MSD, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and Novartis.