Abstract

Background: IL-17 inhibitor is recommended as the commonly used first line treatment option for patients with r-axspa[1]. Ixekizumab, a high-affinity interleukin 17A (IL-17A) inhibitor, demonstrated its efficacy in two international phase 3 r-axSpA clinical trials (COAST-V and COAST-W) [2-4]. Ixekizumab also provided clinical benefits regardless of baseline inflammation status [5]. Here, we report the treatment outcome from a phase 3 trial conducted in Chinese patients with r-axSpA, focusing on patient-reported outcomes (PROs) and spinal mobility. Objectives: To assess the improvement of ixekizumab on spinal pain, spinal pain at night, stiffness, function, and spinal mobility in Chinese patients with r-axSpA at Week 16. The associations with patients' baseline objective inflammation status (normal or elevated C-reactive protein [CRP] level) were also evaluated. Methods: A phase 3, randomized, double-blind, placebo (PBO)-controlled trial (NCT04285229) enrolled both biologic-naive and tumor necrosis factor inhibitor (TNFi)-experienced Chinese patients with r-axSpA. Patients were treated with ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or PBO (1:1) for a 16-week blinded induction period, followed by a 36-week, open-label (IXEQ4W), extended treatment period [5]. PRO endpoints included spinal pain and spinal pain at night evaluated by Numeric Rating Scale (NRS); stiffness measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions 5 and 6; function evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI). Spinal mobility was measured by Bath Ankylosing Spondylitis Metrology Index (BASMI) linear score. Changes from baseline at Week 16 were analyzed using a mixed model for repeated measures (MMRM) including treatment, baseline CRP status, TNFi experience, baseline value, visit, baseline value-by-visit, and treatment-by-visit as fixed effects. Post hoc subgroup analyses were conducted by baseline CRP level (≤ 5 mg/L [normal] vs. > 5 mg/L [elevated]) using Week 0 - 16 data. Treatment group differences were evaluated within each category of the subgroup using MMRM mentioned above (without baseline CRP status). Moreover, an exploratory interaction analysis was performed using MMRM mentioned above with treatment*visit*subgroup as an additional fixed effect. p < 0.05 was considered statistically significant. Results: Baseline characteristics were generally similar between IXEQ4W and PBO groups [6]. Compared with PBO, patients treated with IXEQ4W had significantly greater improvements in changes from baseline (least squares mean [LSM]) in spinal pain, spinal pain at night, stiffness, BASFI, and Linear BASMI at Week 16 (all p <0.05, Figure.1). Subgroup analyses demonstrated IXEQ4W provided greater improvement than PBO in changes from baseline (LSM) at Week 16 in these PRO endpoints irrespective of the baseline CRP level (all p<0.05 except for BASFI [p=0.095] and BASMI [p=0.268] in baseline CRP level > 5 mg/L subgroup, Figure 2B). Treatment-by-subgroup interaction at Week 16 for the baseline CRP level (≤ 5 mg/L vs. > 5 mg/L) did not reach significance for any of these PRO endpoints (all p ≥ 0.05). Conclusion: Compared with PBO, IXEQ4W significantly improved the spinal pain, spinal pain at night, function, and spinal mobility in Chinese patients with r-axSpA. Regardless of the baseline inflammation status (measured by CRP level), the consistent efficacy was observed. These results were consistent with those in COAST-V and COAST-W trials. REFERENCES: [1] Ramiro S et al. Ann Rheum Dis. 2023;82(1):19-34. [2] Mease P et al. Rheumatol Ther. 2019;6(3):435-450. [3] Deodhar AA et al. BMC Rheumatol. 2021;5(1):35. [4] Kiltz U et al. J Rheumatol. 2021;48(2):188-197. [5] Kurt de Vlam et al. EULAR. 2021 [6] Xue Y et al. BioDrugs. Published online September 22, 2023. Acknowledgements: NIL. Disclosure of Interests: Hejian Zou Eli Lilly and Company, Xiaoxia Zhu: None declared, Jiankang Hu: None declared, Dongzhou Liu: None declared, Jingyang Li: None declared, Lingyun Sun: None declared, Lie Dai: None declared, Chunyu Tan: None declared, Zhijun Li: None declared, Zhengyu Xiao: None declared, Yongfu Wang: None declared, Lingli Dong: None declared, Yan Yan Eli Lilly and Company, Eli Lilly and Company, Hongying Li Eli Lilly and Company, Eli Lilly and Company.