Translating Improvements with Ixekizumab in Clinical Trial Outcomes into Clinical Practice: ASAS40, Pain, Fatigue, and Sleep in Ankylosing Spondylitis
Bibliographic record
Abstract
INTRODUCTION: Ixekizumab, a humanized interleukin-17A antibody, has shown efficacy in ankylosing spondylitis (AS), with a greater proportion of ixekizumab-treated patients achieving an ASAS40 (Assessment of Spondyloarthritis International Society 40) endpoint compared to placebo. An ASAS40 response is a high standard that is not routinely used in clinical practice. The goals of this study were (a) to measure improvement in ixekizumab-treated patients in the four ASAS treatment response domains and in other patient-reported outcomes, and (b) to determine how the ASAS response was associated with changes in spinal pain at night, fatigue, sleep, and the Short Form 36-Item Physical Component Summary (SF-36 PCS). METHODS: The COAST-V and COAST-W trials were randomized, double-blind, controlled trials examining ixekizumab efficacy in patients with AS who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced, respectively. Data for the ASAS treatment response domains and other outcomes were collected through 16 weeks. Comparisons between treatment groups were made using a mixed-effects model for repeated measures. To determine how the ASAS response was associated with the changes in spinal pain at night, fatigue, sleep, and SF-36 PCS, comparisons were made between patient groups according to their level of treatment response (ASAS40 vs. ASAS20 vs. ASAS20 nonresponse) using analysis of covariance. RESULTS: Compared with placebo, patients treated with ixekizumab reported significantly greater improvement in the four ASAS treatment response domains and other outcomes (p < 0.05). Results were consistent for bDMARD-naïve and TNFi-experienced patients. Compared to ASAS20 nonresponders, patients who achieved ASAS40 reported significantly greater mean changes in spinal pain at night (1.0 vs. 5.1 for bDMARD-naïve; 0.5 vs. 5.4 for TNFi-experienced), fatigue (0.6 vs. 3.8 for bDMARD-naïve; 0.2 vs. 3.9 for TNFi-experienced), sleep quality (1.1 vs. 4.0 for bDMARD-naïve; 0.8 vs. 4.9 for TNFi-experienced), and SF-36 PCS (2.6 vs. 11.6 for bDMARD-naïve; 1.2 vs. 12.6 for TNFi-experienced) (p < 0.0001). CONCLUSION: Patients with AS who were treated with ixekizumab reported greater improvements in multiple patient-reported outcomes than patients who received placebo. Importantly, achieving ASAS40 was associated with a 2.6-fold to 5.3-fold greater improvement in pain, fatigue, sleep, and quality of life for bDMARD-naïve patients, and a 5.1-fold to 18.5-fold greater improvement for TNFi-experienced patients, compared to ASAS20 nonresponders. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02696785 and NCT02696798. FUNDING: Eli Lilly and Company.
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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 | 0.080 | 0.105 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| 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".