PUB - Publikationen an der Universität Bielefeld

Background/Aims The recommended treatment target for axial spondyloarthritis (axSpA) is remission/low disease activity (LDA) according to Ankylosing Spondylitis Disease Activity Score (ASDAS) levels (ASDAS<2.1); however, remission is difficult to achieve for many patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) remains commonly used in clinical practice to assess disease activity, although limited data exist to validate cut-offs. Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ has demonstrated consistent and sustained efficacy up to Week (Wk)52 in the BE MOBILE 1 and 2 phase 3 studies, including achievement of LDA according to ASDAS by>50% of patients with non-radiographic (nr-)axSpA and radiographic (r-)axSpA. Here, we report achievement of LDA, as assessed by either ASDAS<2.1, BASDAI<4, or both, to Wk52 with BKZ across the spectrum of axSpA in two phase 3 studies. Methods BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743) comprised a 16-wk placebo (PBO)-controlled and 36-wk maintenance period. BE MOBILE 1 (nr-axSpA) patients met Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective inflammation (MRI and/or elevated C-reactive protein). BE MOBILE 2 (r-axSpA) patients met modified New York and ASAS classification criteria. All patients had active disease (BASDAI >= 4 and spinal pain >= 4 [BASDAI item 2]) at baseline. Patients were randomised to subcutaneous BKZ 160mg every 4 weeks (Q4W) or PBO. Patients randomised to PBO switched to BKZ from Wk16 ('PBO/BKZ-switchers'). The proportion of patients that achieved LDA to Wk52, as defined by either ASDAS<2.1, BASDAI<4, or both, are presented (non-responder imputation). Results Overall, 254 patients with nr-axSpA (BKZ: 128/PBO: 126) and 332 with r-axSpA (BKZ: 221/PBO: 111) were randomised. Most had high (ASDAS >= 2.1-<= 3.5) or very high (ASDAS>3.5) disease activity at baseline (nr-axSpA: BKZ: 99.2%/PBO: 97.6%; r-axSpA: BKZ: 98.6%/PBO: 100%). At Wk16, a greater proportion of BKZ vs PBO-treated patients achieved ASDAS<2.1 (nr-axSpA: BKZ: 46.1%/PBO: 19.8%; r-axSpA: BKZ: 42.1%/PBO: 17.1%), BASDAI<4 (nr-axSpA: BKZ: 52.3%/PBO: 31.7%; r-axSpA: BKZ: 55.7%/PBO: 41.4%) and both (nr-axSpA: BKZ: 43.8%/PBO: 19.0%; r-axSpA: BKZ: 41.6%/PBO: 17.1%). Results were sustained/improved across continuous BKZ-treated patients and PBO/BKZ-switchers to Wk52, with achievement of ASDAS<2.1 (nr-axSpA: BKZ: 53.9%/switchers: 47.6%; r-axSpA: BKZ: 50.2%/switchers: 61.3%), BASDAI<4 (nr-axSpA: BKZ: 60.2%/switchers: 54.0%; r-axSpA: BKZ: 65.6%/switchers: 68.5%) and both (nr-axSpA: BKZ: 49.2%/switchers: 45.2%; r-axSpA: BKZ: 49.8%/switchers: 58.6%). Achievement of BASDAI<4 was consistently higher than ASDAS<2.1, regardless of treatment arm. Conclusion Across the full axSpA disease spectrum, BKZ resulted in rapid achievement of LDA vs PBO to Wk16, as assessed by ASDAS<2.1, BASDAI<4, or both; improvements continued to Wk52. Most patients achieving ASDAS<2.1 also achieved BASDAI<4. These data suggest ASDAS<2.1 is a more stringent criterion for LDA, relevant for consideration of BKZ in the context of a potential treat-to-target approach for axSpA in daily practice. Disclosure X. Baraliakos: Consultancies; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma ; grant/research support from: Novartis and UCB Pharma. Member of speakers' bureau; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. Other; Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. S. Ramiro: Grants/research support; AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; Consultant for AbbVie, Eli Lilly, Novartis, Pfizer, Sanofi and UCB Pharma. M. Magrey: Consultancies; AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, BMS and UCB Pharma. M. Rudwaleit: Consultancies; AbbVie, Eli Lilly, Novartis and UCB Pharma. Member of speakers' bureau; AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. N. Haroon: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. C. Fleurinck: Other; Employees of UCB Pharma. U. Massow: Other; Employees of UCB Pharma. N. de Peyrecave: Other; Employees of UCB Pharma. T. Vaux: Other; Employees of UCB Pharma. H. Marzo-Ortega: Consultancies; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Honoraria; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Grants/research support; Janssen, Novartis and UCB Pharma. V. Navarro-Compan: Consultancies; AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma. Member of speakers' bureau; AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie and Novartis.