POS0806 LONG-TERM SUSTAINED EFFICACY AND SAFETY OF BIMEKIZUMAB ACROSS THE FULL SPECTRUM OF AXIAL SPONDYLOARTHRITIS: 2-YEAR RESULTS FROM TWO PHASE 3 STUDIES
Authors: X. Baraliakos, A. Deodhar, D. Van der Heijde, F. Van den Bosch, M. Magrey, W. P. Maksymowych, T. Tomita, H. Xu, U. Massow, C. Fleurinck, T. Vaux, C. Prajapati, J. Shepherd-Smith, A. Marten, L. S. Gensler
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has shown efficacy and safety to 1 year (yr) in patients (pts) with active non-radiographic (nr-) and radiographic axial spondyloarthritis (r-axSpA; or ankylosing spondylitis) [1] in the phase 3 studies, BE MOBILE 1 and 2, respectively. [2,3] <h3>Objectives:</h3> To assess 2-yr efficacy and safety of BKZ in these pts. <h3>Methods:</h3> In BE MOBILE 1 (NCT03928704) and 2 (NCT03928743) pts were randomised to subcutaneous BKZ 160 mg every 4 weeks (wks; Q4W) or placebo (PBO); all pts received BKZ 160 mg Q4W from Wk 16 to 52. On completion at Wk 52, pts could enter BE MOVING (NCT04436640); an ongoing, open-label extension (OLE) study. Efficacy outcomes are reported for pts with nr-/r-axSpA from BE MOBILE 1 and 2 and the combined OLE up to 2 yrs (104 wks; N=586). Data are reported using non-responder imputation (NRI; binary outcomes), multiple imputation (MI; continuous outcomes) and observed cases (OC). Data are reported for the randomised set; pts not enrolled in the OLE were imputed as non-responders. Pooled safety data are reported up to 2 yrs for all pts who received BKZ (N=574). <h3>Results:</h3> Of 254 nr-axSpA pts and 332 r-axSpA pts originally randomised to BKZ or PBO in BE MOBILE 1 and 2, respectively, 494 pts entered BE MOVING at Wk 52. By July 2023, 189 nr-axSpA and 267 r-axSpA pts completed Wk 104. 1-yr efficacy was sustained to 2 yrs in both nr-/r-axSpA populations (Figure 1; Table 1). [3] Assessment of SpondyloArthritis international Society 40% (ASAS40) responses were maintained from Wk 52 to 104 (<b>nr-axSpA</b>: 55.9% to 49.2% [NRI]; 65.1% [142/218] to 66.1% [125/189; OC]; <b>r-axSpA</b>: 61.7% to 53.9% [NRI]; 68.8% [205/298] to 67.0% [179/267; OC]). At Wk 104, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA; &lt;2.1) was achieved by 61.2% and 63.4% of pts with nr-/r-axSpA, respectively (MI). ASDAS inactive disease (ASDAS &lt;1.3) and ASAS partial remission were achieved and maintained by roughly a third of pts at Wk 104 (ASDAS &lt;1.3 [MI]: <b>nr-axSpA</b>: 31.6%; <b>r-axSpA</b>: 31.3%; ASAS partial remission [NRI]: <b>nr-axSpA</b>: 30.7%; <b>r-axSpA</b>: 31.3%). BKZ treatment led to sustained inflammation suppression, demonstrated by hs-CRP levels in both pt populations. To Wk 104, 89.5% (514/574) of pts with axSpA had ≥1 treatment-emergent adverse event (TEAE) on BKZ; the most frequent TEAEs by preferred term (exposure-adjusted incidence rate per 100 pt-yrs [EAIR/100 PY]; MedDRA v19.0) were SARS-CoV-2 infection (COVID-19; 13.2), nasopharyngitis (10.2), and upper respiratory tract infection (6.0). EAIR/100 PY of serious TEAEs was low (5.4); no major adverse cardiovascular events, active tuberculosis cases, serious SARS-CoV-2 infections, anaphylaxis, or deaths were reported. Incidence of suicidal ideation and behaviour was low (EAIR/100 PY: 0.1). Hepatic events occurred in 72 patients (EAIR/100 PY: 5.5); most had liver function test elevations or transient abnormalities (n=53; no cases of confirmed Hy's law). Malignancy rates were low (EAIR/100 PY: 0.5). Of 122 pts who experienced fungal infections (21.3%; EAIR/100 PY: 10.0), 76 had <i>Candida</i> infections (13.2%; EAIR/100 PY: 5.8 – mostly oral); almost all were mild–moderate and none were serious/systemic – 6 cases led to study discontinuation. <i>Tinea</i> infections (2.8%; EAIR/100 PY: 1.1) and fungal infections not elsewhere classified, such as oral, skin, and vulvovaginal infections (8.5%; EAIR/100 PY: 3.6) were less common. Incidence of IBD (EAIR/100 PY: 0.6) and uveitis (EAIR/100 PY: 1.6) was low. To Wk 104, most EAIRs of the above TEAEs were similar to or lower than those reported to Wk 52; no new safety signals were observed. <h3>Conclusion:</h3> Across the full disease spectrum of axSpA, BKZ had sustained efficacy to 2 yrs. No new safety signals were observed, consistent with the safety profile established in prior studies. [3] <h3>REFERENCES:</h3> [1] Boel A. Ann Rheum Dis 2019;78(11):1545–49. [2] van der Heijde D. Ann Rheum Dis 2023;82(4):515–26. [3] Baraliakos X. Ann Rheum Dis 2023;10.1136/ard-2023-224803. <h3>Acknowledgements:</h3> Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma. <h3>Disclosure of Interests:</h3> Xenofon Baraliakos Paid instructor for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma, Speaker for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, and UCB Pharma, Consultant for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma, Grant/research support from Novartis and UCB Pharma, Atul Deodhar Speaker for Eli Lilly, Janssen, Novartis and Pfizer and UCB Pharma, Consultant for AbbVie, BMS, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from BMS, Celgene, Eli Lilly, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Director of Imaging Rheumatology BV, Consultant for AbbVie, Bayer, BMS, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Takeda and UCB Pharma, Filip van den Bosch Speaker for AbbVie, Amgen, Janssen, Merck, Novartis, Pfizer and UCB Pharma, Consultant for AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Marina Magrey Consultant for AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma, Research grants from AbbVie, BMS and UCB Pharma, Walter P Maksymowych Chief Medical Officer for Canadian Research and Education (CARE) Arthritis, Honoraria/consulting fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from AbbVie, Pfizer and UCB Pharma, educational grants from AbbVie, Janssen, Novartis and Pfizer, Tetsuya Tomita Speaker for AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer, Consultant for AbbVie, Eli Lilly, Gilead, Novartis and Pfizer, Huji Xu Speaker for AbbVie, Janssen, Novartis, Pfizer and UCB Pharma, Clinical investigator for Peking-Tsinghua Center for Life Sciences, Consultant for AbbVie, Beigene, BioMap, IASO, Pfizer and UCB Pharma, Ute Massow Employee of UCB Pharma, Carmen Fleurinck Shareholder of UCB Pharma, Employee of UCB Pharma, Tom Vaux Employee of UCB Pharma, Chetan Prajapati Employee of Veramed LTD, Julie Shepherd-Smith Employee of UCB Pharma, Alexander Marten Employee of UCB Pharma, Lianne S Gensler Consultant for AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from Novartis and UCB Pharma paid to institution.