P194 Response to ixekizumab by C-reactive protein level in patients with aadiographic axial spondyloarthritis: results from the COAST-V (biological-naïve) and COAST-W (TNF-α inhibitor-experienced) trials at 52 weeks
Bibliographic record
Abstract
Abstract Background/Aims Tumor necrosis factor inhibitors (TNFis) are effective treatments for radiographic axial spondyloarthritis (r-axSpA), but may be less effective in patients (pts) without elevated C-reactive protein (CRP). This study evaluated the efficacy of ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A, in pts with r-axSpA at 52 weeks (wks) with nonelevated (≤5mg/L) and elevated (>5mg/L) baseline (BL) CRP. Methods COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomised, double-blind, PBO-controlled trials investigating efficacy of 80-mg IXE every 4 wks and every 2 wks in pts who met ASAS criteria for raxSpA, had radiographic sacroiliitis according to mNY criteria, and were biological diseasemodifying antirheumatic drug (bDMARDs)-naïve (COAST-V) or TNFiexperienced (COAST-W). Data from 157 COAST-V pts and 188 COAST-W pts treated with IXE from Wk0 to 52 were analyzed. Patients were stratified based on nonelevated (≤5mg/L) vs elevated (>5 mg/L) BL CRP. Additional analysis was done with BL CRP ≤10.0mg/L vs > 10.0mg/L. Efficacy was assessed by ASAS40, ≥50% improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), and change in Short Form 36 physical component summary (SF36 PCS) score. Missing data were imputed by nonresponder imputation for binary measures and modified BL observation carried forward for continuous measure. Week 16 data are presented for comparison. Results Of pts treated with IXE through Wk52, 34.4% had CRP ≤5.0mg/L, 65.6% had CRP >5.0mg/L, 61.8% had CRP ≤10.0mg/L, and 38.2% had CRP >10.0mg/L at BL in COASTV and 33.0% had CRP ≤5.0mg/L, 67.0% had CRP >5.0mg/L, 55.9% had CRP ≤10.0mg/L, and 44.1% had CRP >10.0mg/L at BL in COAST-W.At Wk16, the proportion of pts achieving ASAS40 in COAST-V was numerically higher with IXE in the ≤5mg/L group and significantly higher with IXE in the >5mg/L group vs PBO, as previously shown, and was significantly higher with IXE in the ≤10mg/L and >10mg/L groups vs PBO. Results were similar in COAST-W and significant in the >5mg/L and ≤10mg/L groups vs PBO. At Wk52, greater than 45% of COAST-V pts and greater than 35% of COAST-W pts treated with IXE achieved an ASAS40 response, greater than 40% of COAST-V pts and greater than 25% of COAST-W patients treated with IXE achieved a BASDAI50 response, and change from baseline in SF-36 PCS score in patients treated with IXE was greater than 5 points in both studies regardless of the BL CRP cutoffs evaluated. Conclusion A higher proportion of ASAS40 responders was observed in IXE treated arms versus PBO among bDMARD-naïve and TNFi-experienced pts with r-axSpA when the CRP cutoff of 10mg/L was evaluated, and the responses were consistent through Wk52. Furthermore, similar proportions of pts achieved BASDAI50 and SF-36 responses within each patient population regardless of the BL CRP cutoff evaluated. Disclosure J.D. Reveille: None. P. Rahman: None. D.M. Sandoval Calderon: Shareholder/stock ownership; D. Sandoval Calderon is a shareholder and employee of Eli Lilly and Company. T. Muram: Shareholder/stock ownership; T. Muram is a shareholder and employee of Eli Lilly and Company. A. Kronbergs: Shareholder/stock ownership; A. Kronbergs is a shareholder and employee of Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; R.Bolce is a shareholder and employee of Eli Lilly and Company. V. Geneus: Shareholder/stock ownership; V. Geneus is a shareholder and employee of Eli Lilly and Company. T. Hunter: Shareholder/stock ownership; T. Hunter is a shareholder and employee of Eli Lilly and Company. S. Liu-Leage: Shareholder/stock ownership; S.L. League is a shareholder and employee of Eli Lilly and Company. M. Rudwaleit: None. J.A. Maldonado-Cocco: None. F. van den Bosch: None.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".