Translating Improvements with Ixekizumab in Clinical Trial Outcomes into Clinical Practice: ASAS40, Pain, Fatigue, and Sleep in Ankylosing Spondylitis
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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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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 | 0.002 | 0.000 |
| 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 | 0.000 |
| 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 it