Does HLA-B27 Status Influence Ixekizumab Efficacy in Axial Spondyloarthritis? Results From the COAST-V, COAST-W, and COAST-X Trials

Authors

John D Reveille
Martin Rudwaleit
Proton Rahman
Jose A Maldonado-Cocco
Marina Magrey
Rebecca Bolce
Khai Jing Ng
Theresa Hunter Gibble
Jeffrey Lisse
So Young Park
Andris Kronbergs
Victoria Navarro-Compán

Language

English

Publication Date

2-1-2026

Journal

Rheumatology and Therapy

DOI

10.1007/s40744-025-00810-5

PMID

41417207

PMCID

PMC12816414

PubMedCentral® Posted Date

12-19-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Introduction: The human leukocyte antigen (HLA)-B27 is associated with axial spondyloarthritis (axSpA) and is a predictor of response to tumor necrosis factor inhibitors. However, limited data are available on HLA-B27 and interleukin-17 inhibitors. We evaluated the influence of HLA-B27 status on ixekizumab response through 52 weeks in patients with axSpA.

Methods: Data were analyzed from three randomized placebo-controlled trials: COAST-V (NCT02696785), COAST-W (NCT02696798), and COAST-X (NCT02757352). Patients fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria for radiographic (r)-axSpA or non-radiographic (nr)-axSpA. Patients were randomized to receive 80 mg ixekizumab every 2 weeks, 80 mg ixekizumab every 4 weeks, or placebo. This post hoc analysis assessed the intent-to-treat population. The magnitude of benefit was calculated as the value for ixekizumab minus placebo.

Results: Among ixekizumab-treated patients with r-axSpA at week 16, ASAS ≥ 40% improvement (ASAS40) was achieved by 39.6% (n = 118/298) of HLA-B27-positive and 29.3% (n = 12/41) of HLA-B27-negative patients. The magnitude of benefit (ixekizumab-placebo) was 23.5% for HLA-B27-positive and 15.2% for HLA-B27-negative patients. At week 52, 44% of HLA-B27-positive and 31.7% of HLA-B27-negative patients achieved ASAS40. Similar trends were seen for Axial Spondyloarthritis Disease Activity Score low disease activity (ASDAS LDA; < 2.1) and Bath Ankylosing Spondylitis Disease Activity Index ≥ 50% improvement (BASDAI50). In ixekizumab-treated patients with nr-axSpA at week 16, ASAS40 response was achieved by 41.7% (n = 55/132) of HLA-B27-positive and 28.0% (n = 14/50) of HLA-B27-negative patients. The magnitude of benefit was 19.2% for HLA-B27-positive and 16.0% for HLA-B27-negative patients. At week 52, 52.3% of HLA-B27-positive and 32.0% of HLA-B27-negative patients achieved ASAS40. Similar trends were seen among patients with nr-axSpA for ASDAS LDA and BASDAI50.

Conclusions: In patients with r-axSpA and nr-axSpA, ixekizumab improved response through 52 weeks for both HLA-B27-positive and HLA-B27-negative patients. However, the magnitude of benefit for ixekizumab versus placebo was numerically greater for HLA-B27-positive patients.

Keywords

Axial spondyloarthritis, HLA-B27, Ixekizumab, Non-radiographic, Radiographic

Comments

Trial registration: ClinicalTrials.gov identifiers, NCT02696785, NCT02696798, and NCT02757352.

Published Open-Access

yes

Recommended Citation

Reveille, John D; Rudwaleit, Martin; Rahman, Proton; et al., "Does HLA-B27 Status Influence Ixekizumab Efficacy in Axial Spondyloarthritis? Results From the COAST-V, COAST-W, and COAST-X Trials" (2026). The Brown Foundation: Institute of Molecular Medicine. 57.
https://digitalcommons.library.tmc.edu/molecular_med/57