POS0801 IXEKIZUMAB IMPROVES DISEASE ACTIVITY OF RADIOGRAPHIC-AXIAL SPONDYLOARTHRITIS IN CHINESE PATIENTS IRRESPECTIVE OF BASELINE OBJECTIVE INFLAMMATION STATUS

Background:

Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory disease which predominantly affects the spine and sacroiliac joints (SIJ) [1]. Ixekizumab, a high-affinity interleukin 17A (IL-17A) inhibitor, demonstrated efficacy (Assessment of SpondyloArthritis International Society 40 [ASAS40] response at Week 16) irrespective of elevated or normal/low inflammation at baseline [2]. The association of baseline inflammation status with efficacy endpoints in Chinese r-axSpA population has not been investigated.

Objectives:

To evaluate the association of the efficacy of ixekizumab in disease activity through Week 52 with the objective baseline inflammation status (measured by baseline c-reactive protein [CRP] level, Spondyloarthritis Research Consortium of Canada [SPARCC] magnetic resonance imaging [MRI] spine or SIJ inflammation score) in Chinese patients with r-axSpA.

Methods:

Chinese patients with r-axSpA, biologic-naive or tumor necrosis factor inhibitor (TNFi)-experienced, were enrolled in a phase 3, randomized, double-blind, placebo-controlled study (NCT04285229) and randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo (PBO) for 16 weeks. At Week 16, patients receiving PBO were switched to IXEQ4W, and those receiving IXEQ4W continued, until Week 52. Subgroup analyses were performed through Week 52 for the intent-to-treat population by baseline CRP level (normal/low [≤5 mg/L] or elevated [>5 mg/L]), SPARCC MRI spine or SIJ inflammation score(<2 or ≥2). Baseline MRI was available in 98.6% of patients by central reading. Endpoints included response rates of ASAS40, Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50), Ankylosing Spondylitis Disease Activity Score (ASDAS)< 2.1. Non-responder imputation (NRI) was used for imputing missing responses. p-values for treatment comparison were based on Fisher's exact test for Week 0 - 16 data. p < 0.05 was considered statistically significant. Week 20-52 data were summarized descriptively.

Results:

Baseline characteristics were balanced between IXEQ4W and PBO groups [3]. Analyses results demonstrated that IXEQ4W provided significant improvement in ASAS40, BASDAI50, and ASDAS < 2.1 response rates compared with PBO at Week 16 within subgroups (except for ASAS40,BASDAI50, and ASDAS < 2.1 response rates within baseline SPARCC MRI spine score <2 subgroup [p=0.088, 0.104, and 0.203, respectively]) and efficacy sustained through Week 52, irrespective of the baseline CRP level, SPARCC MRI spine or SIJ score (Table 1 and Figure 1). Significant differences between IXEQ4W and PBO in the ASDAS < 2.1 response rates were observed as early as Week 1 across most of the subgroups (except for baseline SPARCC MRI spine score <2). Regardless of the baseline CRP level, SPARCC MRI spine or SIJ score, patients who initially received IXEQ4W had sustained improvements in ASDAS<2.1 response through Week 52; patients randomized to receive PBO and switched to IXEQ4W at Week 16 reported a rapid and sustained improvement through Week 52 after switching (Figure 1).

Conclusion:

IXEQ4W demonstrated rapid and sustained improvement in disease activity in Chinese patients with r-axSpA through Week 52 irrespective of baseline elevated or normal/low inflammation measured by CRP level, SPARCC MRI spine or SIJ score. These subgroup analyses results were generally consistent with those from overall population.

REFERENCES:

[1] Navarro-Compán V, Sepriano A, El-Zorkany B, van der Heijde D. Axial spondyloarthritis. Ann Rheum Dis. 2021;80(12):1511-1521. doi:10.1136/annrheumdis-2021-221035 [2] Maksymowych WP, Bolce R, Gallo G, et al. Ixekizumab in radiographic axial spondyloarthritis with and without elevated C-reactive protein or positive magnetic resonance imaging. Rheumatology (Oxford). 2022;61(11):4324-4334. doi:10.1093/rheumatology/keac104 [3] Xue Y, Hu J, Liu D, et al. Ixekizumab for Active Radiographic Axial Spondyloarthritis in Chinese Patients: 16- and 52-Week Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study. BioDrugs. Published online September 22, 2023. doi:10.1007/s40259-023-00625-2

Acknowledgements:

NIL.

Disclosure of Interests:

Ning Kong: 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, Lijun Wu: None declared, Yan Yan Eli Lilly and Company, Eli Lilly and Company, Hongying Li Eli Lilly and Company, Eli Lilly and Company, Hejian Zou Eli Lilly and Company.