CONFERENCE UPDATE: EULAR 2024

Impact of ixekizumab on structural lesions in SIJ of patients with r-axSpA: Post-hoc analysis of the COAST-V trial

RHEUMATOLOGY
22 Aug 2024

STUDY DESIGN

Ixekizumab (IXE) is a monoclonal antibody that selectively inhibits interleukin (IL)-17A, which plays a pivotal role in the pathogenesis of radiographic axial spondyloarthritis (r-axSpA).1 Previously, IXE has been demonstrated to improve signs and symptoms of r-axSpA, but the effect of IXE on structural lesions in the sacroiliac joints (SIJ) of r-axSpA patients remains unknown.1

COAST-V is a 52-week phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled and active-controlled trial involving bio-naïve adult patients with active r-axSpA (n=341).1 They were randomized 1:1:1:1 to receive PBO, 80mg subcutaneous IXE every 2 weeks (Q2W), IXE every 4 weeks (Q4W), or 40mg adalimumab (ADA) Q2W as an active reference.1 In week 16, patients in the PBO and ADA groups were randomized 1:1 again to receive IXE Q2W or Q4W.1

This post-hoc analysis evaluated the effect of IXE on structural lesions in SIJ at baseline, week 16, and week 52.1 The effect of IXE was evaluated by changes in magnetic resonance imaging (MRI) structural lesions as assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint structural scores (SSS) for 4 lesion types including erosion, backfill, fat metaplasia, and ankylosis.1 After adjusting for baseline SPARCC values, baseline SPARCC bone marrow edema (BME) and stratification factors, covariance analysis was conducted to compare treatments based on observed data for each type of lesion.1 Sensitivity analyses were adjusted for different baseline factors and subsets of patients with less severe ankylosis scores.1 Changes in structural lesions were stratified by sex, HLA-B27 status, and SPARCC BME baseline cutoffs of ≥4 and <4 for subgroup analyses.1

FINDINGS

Efficacy outcomes:
  • The key outcomes measured in this analysis included changes in 4 types of MRI structural lesions including erosion, backfill, fat metaplasia, and ankylosis1
  • At week 16, a significant decrease in SPARCC SSS erosion score compared PBO was observed with both IXE doses, with the greatest decrease seen with IXE Q2W (least squares mean [LSM]: -0.91; p≤0.001)1
  • At week 16, the SPARCC SSS backfill scores saw notable increases with both doses of IXE, but the increase was only significant with the Q2W regimen (LSM: 0.52; p≤0.001)1
  • From week 16 through to week 52, SPARCC SSS showed continued reductions in erosion and increases in backfill1
  • Switching from PBO to IXE led to a significant reduction of SPARCC SSS in erosion and an increase in backfill to similar levels to the IXE arms1

Subgroup analyses:
  • Subgroup analyses were conducted on changes in structural lesions by sex, HLA-B27 status and SPARCC BME baseline cutoffs of ≥4 and <41
  • A greater reductive impact on SPARCC SSS erosion scores in males than in females was found with IXE1
  • The effects of IXE were more pronounced than PBO in HLA-B27 negative populations in SPARCC SSS in erosion (-2.556 vs. 0.015; p<0.01) and backfill (2.684 vs. -0.003; p<0.001)1
  • In patients with SPARCC SIJ BME ≥4, IXE showed a significantly greater impact on all types of lesions, except ankylosis1

 

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