Does HLA-B27 Status Influence Ixekizumab Efficacy in Axial Spondyloarthritis? Results From the COAST-V, COAST-W, and COAST-X Trials
Bibliographic record
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. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT02696785, NCT02696798, and NCT02757352.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".