PUB - Publikationen an der Universität Bielefeld

Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ has demonstrated sustained efficacy to Week 52 in patients with non-radiographic (nr-) and radiographic (r-)axial spondyloarthritis (axSpA) in the phase 3 studies BE MOBILE 1 and 2.[1,2] Studies have shown that male and female patients with axSpA can experience different disease manifestations, clinical burden and treatment efficacy. For example, female patients typically have delayed diagnosis and higher disease burden but less radiographic progression.[3] Objectives: To assess the efficacy of BKZ treatment to Week 52 in patients across the full disease spectrum of axSpA, focusing on potential sex-based differences in treatment response. Methods: BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743) both comprised a 16-week double-blind period followed by a 36-week maintenance period. In both studies, patients were randomised to receive subcutaneous BKZ 160 mg every 4 weeks (Q4W) or placebo (PBO); from Week 16, all patients received BKZ 160 mg Q4W. We report efficacy outcomes from the BE MOBILE studies to Week 52, stratified by sex. Outcomes reported include ASAS40, ASDAS <2.1, BASDAI, Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) and objective signs of inflammation (OSI; MRI SPARCC SIJ, MRI Berlin spine and hs-CRP). Binary endpoints are presented using non-responder imputation and continuous outcomes are reported using multiple imputation; OSI measures are reported using observed case. To compare BKZ vs PBO efficacy (treatment effect) between male vs female patients at Week 16, adjusted relative odds ratios (rOR) and relative differences (RD) were calculated using logistic regression and ANCOVA, respectively. All rOR and RD analyses were adjusted for region, age, HLA-B27 status and, for the continuous endpoints, their baseline values. Additionally, in patients with nr-axSpA, analyses were adjusted for MRI/CRP classification and, in patients with r-axSpA, for prior TNF inhibitor exposure and hs-CRP. Since all analyses were post-hoc, no formal p values are provided. Results: 254 patients with nr-axSpA were randomized in BE MOBILE 1 and 332 patients with r-axSpA were randomized in BE MOBILE 2; of these, 220/254 (male: 124/138 [89.9%]; female: 96/116 [82.8%]) and 298/332 (male: 215/240 [89.6%]; female: 83/92 [90.2%]) completed to Week 52. Key baseline differences between males and females included longer mean symptom duration (years) in females (nr-axSpA: 7.2 vs 11.1; r-axSpA: 12.9 vs 15.0) and lower HLA-B27 positivity (%) in females (nr-axSpA: 84.8 vs 69.0; r-axSpA: 88.3 vs 78.3). Across BKZ and PBO-randomised patients, males had lower mean ASQoL scores vs females (nr-axSpA: BKZ: 8.5 vs 10.8, PBO: 8.6 vs 10.2; r-axSpA: BKZ: 8.3 vs 11.1, PBO: 8.4 vs 9.0), and generally had higher OSI values at baseline. Across ASAS40, ASDAS <2.1 and BASDAI, there was a pattern of higher BKZ vs PBO treatment effect in males vs females at Week 16, which was reflected in the rORs and RDs at this timepoint (Figure 1). At Week 52, response rates were higher in males vs females with nr-axSpA but comparable in patients with r-axSpA. Overall, at Week 52 both males and females responded well in both trials, with >50% of BKZ-randomized patients achieving ASAS40 (nr-axSpA: 64.4 vs 56.4; r-axSpA: 59.4 vs 55.7), and >40% achieving ASDAS <2.1 (nr-axSpA: 72.0 vs 47.4; r-axSpA: 57.7 vs 55.8). BKZ-randomised males and females also showed good overall response in mean improvements in BASDAI scores at Week 52 (nr-axSpA: −4.0 vs −3.6; r-axSpA: −3.6 vs −3.4; Figure 1). For ASQoL, both males and females demonstrated substantial improvements with BKZ treatment at Week 16 (nr-axSpA: −5.5 vs −4.8; r-axSpA: −4.8 vs −5.5) compared with PBO treatment (nr-axSpA: −2.1 vs −2.9; r-axSpA: −3.1 vs −3.7). Improvements continued to Week 52 with BKZ treatment (nr-axSpA: BKZ: −5.7 vs −6.2, PBO/BKZ: −5.5 vs −5.1; r-axSpA: BKZ: −5.4 vs −6.5, PBO/BKZ: −5.5 vs −5.8). For change from baseline in OSI outcomes, RDs generally indicated a higher BKZ vs PBO treatment effect in males vs females at Week 16 (Figure 2). However, absolute OSI values in males and females were generally comparable at Week 16, with values maintained or improved to Week 52 with BKZ treatment (Figure 2). Conclusion: The treatment effect of BKZ vs PBO at Week 16 tended to be higher among male patients with axSpA compared to their female counterparts. However, at Week 52 female patients showed marked improvement in longer-term treatment response to BKZ, with efficacy comparable to those seen in male patients at this timepoint. Overall, the efficacy of BKZ in clinical, patient-reported, and OSI outcomes was demonstrated in both male and female patients across the full disease spectrum of axSpA.