Efficacy of Ixekizumab in Radiographic Axial Spondyloarthritis by Baseline C-Reactive Protein Level: A Pooled Analysis of Phase III Trials

INTRODUCTION: C-reactive protein (CRP) predicts radiographic progression in radiographic axial spondyloarthritis (r-axSpA). Normal CRP levels have been associated with reduced response to tumor necrosis factor inhibitor treatment. Ixekizumab (IXE) has demonstrated effectiveness in smaller patient groups stratified by CRP at baseline. This pooled analysis aims to demonstrate efficacy stratified by CRP across a broader population. METHODS: This post hoc analysis pooled biologic-naïve patients with r-axSpA from two phase III trials: COAST-V (N = 168) and NCT04285229 (N = 130), with participants receiving IXE 80 mg every 4 weeks or placebo for up to 52 weeks. Analyses evaluated outcomes in patients stratified by CRP at baseline (≤ 5 mg/L or > 5 mg/L). A second analysis subgrouped patients based on magnetic resonance imaging (MRI)-detected inflammation in the spine or sacroiliac joints (SIJ). RESULTS: Baseline characteristics were comparable between normal (N = 105 35.2%) and elevated CRP (N = 193 64.8%) groups, except for corticosteroid use, MRI-SPARCC spine and SIJ total scores, and ASDAS. Across groups, 67.8-81.8% of patients had MRI inflammation. By week 52, IXE demonstrated improvements in ASAS40 (61.2% normal CRP, 63.0% elevated CRP), ASDAS LDA/ID (69.4% normal CRP, 58.8% elevated CRP), and BASDAI50 (55.1% normal CRP, 63.0% elevated CRP) compared with placebo. Similar improvements were observed across CRP groups for patients with MRI evidence of inflammation at weeks 16 and 52. CONCLUSION: Patients with r-axSpA and normal CRP at baseline have a similar disease burden to those with elevated CRP. IXE provides significant clinical benefits across key outcome measures regardless of CRP level. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02696785 and NCT04285229.