POS0058 IMPACT OF BIMEKIZUMAB ON MRI INFLAMMATORY AND STRUCTURAL LESIONS IN THE SACROILIAC JOINTS OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS: 52-WEEK RESULTS AND POST HOC ANALYSES FROM THE BE MOBILE 1 AND 2 PHASE 3 STUDIES
Authors: W. P. Maksymowych, S. Ramiro, D. Poddubnyy, X. Baraliakos, R. G. Lambert, U. Massow, C. Fleurinck, T. Vaux, C. Prajapati, A. Marten, N. De Peyrecave, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. In the parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies, BKZ demonstrated rapid improvements in efficacy outcomes that were sustained to Week 52 and consistent across the full disease spectrum of axial spondyloarthritis (axSpA; non-radiographic axSpA [nr-axSpA] and radiographic axSpA [r-axSpA; i.e. ankylosing spondylitis][1,2,3]. The impact of dual inhibition of IL-17A and IL-17F on structural lesions in patients with axSpA has not yet been demonstrated. <h3>Objectives:</h3> To evaluate the impact of BKZ on MRI inflammatory and structural lesions in the sacroiliac joints (SIJ) of patients with axSpA to Week 52 in BE MOBILE 1 and BE MOBILE 2. <h3>Methods:</h3> BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) study designs have been reported previously.[4] Patients were randomised (1:1 and 2:1, respectively) to subcutaneous BKZ 160 mg every 4 weeks (Q4W) or placebo (PBO). From Week 16, all patients received subcutaneous BKZ 160 mg Q4W. Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation scores and SPARCC SIJ Structural Score (SSS; erosion, backfill, fat, ankylosis) were assessed at baseline, Week 16 and Week 52 in patients in the MRI sub-studies. MRIs were assessed via central reading by two independent expert readers, with an adjudicator in cases of disagreement. Inflammatory and structural lesions were assessed independently by different readers. All readers were blinded to timepoint and any clinical data; structural lesions were analysed post hoc. We report observed case data for patients across the full disease spectrum of axSpA with valid MRI assessments at all 3 timepoints. <h3>Results:</h3> Overall, 60% (152/254) of patients with nr-axSpA and 42% (139/332) of patients with r-axSpA were enrolled in the MRI sub-studies. All sub-study patients with nr-axSpA and 99% (138/139) of patients with r-axSpA had SPARCC inflammation assessments at baseline; 76% (115/152) and 78% (109/139) of patients had valid assessments at all 3 timepoints, respectively. Mean SPARCC inflammation scores were largely comparable between BKZ- and PBO-randomised patients at baseline in patients with nr-axSpA and r-axSpA (<b>Figure 1</b>). Reductions from baseline in mean absolute SPARCC inflammation observed at Week 16 were maintained to Week 52 for continuous BKZ patients; patients who switched from PBO to BKZ at Week 16 (PBO-switchers) reached similar levels of improvement as continuous BKZ patients at Week 52 (<b>Figure 1</b>). For SPARCC SSS, 97% (148/152) of patients with nr-axSpA and all patients with r-axSpA in the MRI sub-studies had assessments at baseline; 84% (128/152) and 83% (116/139) of patients had valid SPARCC SSS assessments at all 3 timepoints, respectively. Reductions from baseline in SPARCC SSS for erosions and increases from baseline in backfill and fat were observed with BKZ versus PBO at Week 16, with further reductions and increases, respectively, to Week 52 in the continuous BKZ group; similar changes were observed in PBO-switchers (<b>Figure 2</b>). No change in SPARCC SSS for ankylosis was observed following treatment with BKZ in patients with nr-axSpA to Week 52 (<b>Figure 2</b>). <h3>Conclusion:</h3> These data, from two parallel phase 3 studies, demonstrated the impact of BKZ on SIJ inflammation and structural lesions across the full disease spectrum of axSpA to Week 52. Dual inhibition of IL-17A and IL-17F with BKZ over 52 weeks of treatment substantially improved MRI inflammation, reduced erosions and increased backfill and fat in the SIJ of patients with nr-axSpA and r-axSpA, which may suggest evidence of tissue repair. <h3>REFERENCES:</h3> [1] Boel A. Ann Rheum Dis 2019;78:1545–9. [2] van der Heijde D. Ann Rheum Dis 2023; ard-2023-225185. [3] Baraliakos X. Ann Rheum Dis 2023; ard-2023-224803. [4] van der Heijde D. Ann Rheum Dis 2023;82(4):515–26. <h3>Acknowledgements:</h3> Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma. <h3>Disclosure of Interests:</h3> Walter P Maksymowych Chief Medical Officer for CARE ARTHRITIS, Honoraria/consulting fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Research grants from AbbVie, Pfizer and UCB Pharma; educational grants from AbbVie, Janssen, Novartis and Pfizer, 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, 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, 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 for AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma, Grant/research support from Novartis and UCB Pharma, Robert G Lambert Consultant for CARE Arthritis and Image Analysis Group, 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, Alexander Marten Employee of UCB Pharma, Natasha de Peyrecave Employee of UCB Pharma, Mikkel Østergaard Speakers bureau for Abbott, BMS, Merck, Mundipharma, Pfizer and UCB Pharma, Consulting fees from Abbott, Pfizer, Merck, Roche and UCB Pharma, Research grants from Abbott, Pfizer and Centocor.