P277 Ixekizumab shows a distinct pattern of pain improvement beyond measurable inflammation as assessed by MRI, CRP or BASDAI questions 5 and 6 in patients with ankylosing spondylitis
Bibliographic record
Abstract
Abstract Background/Aims Efficacy of ixekizumab (IXE) in patients (pts) with ankylosing spondylitis (AS) at week (W) 16 in the absence of elevated inflammation as measured by CRP and MRI Spondyloarthritis Research Consortium of Canada (SPARCC) has been previously reported. In this analysis, we evaluated the improvement in pain with IXE based on longitudinal status of objective measures of inflammation by MRI, CRP value, and BASDAI 5/6 over 16W. Methods The Phase III COAST-V (NCT02696785) 52W, multi-center, randomized, double-blind, placebo (PBO)-controlled study examined the efficacy of IXE in pts with active AS. Adalimumab (ADA) was used as an active reference arm for the first 16W. Pts assigned to ADA went through a wash-out period of 6W prior to getting their first dose of IXE. Change in spinal pain at night (SP-N) and Short Form 36 Health Survey Questionnaire (SF-36) Bodily Pain were measured during study visits and analyzed while controlling for inflammation status using MRI, CRP levels and mean of BASDAI 5/6 (Q5: Duration, Q6: Intensity of morning stiffness). Observed data analyses are presented for each group stratified by treatment arm. Initial analysis: ‘controlled inflammation’ is defined as MRI SPARCC SI joint <4 and MRI SPARCC Spine <3 at W16, CRP <5mg/L at every visit W4-16, or BASDAI 5/6 improvement of ≥ 2 points W12 and W16. Second analysis: control is defined as CRP <5 mg/L at every week between W4-16 and MRI SPARCC SI joint <4 at W16 and MRI SPARCC Spine <3 at W16. Results When inflammation is controlled per MRI, pts treated (tx) with IXEQ4W (-3.9 p<0.001) and ADA (-2.8 p=0.02) experienced significant reduction in SP-N vs PBO (-1.6) at W16; further improvements were experienced in pts rerandomized to IXE by W52. When inflammation was not controlled per MRI, IXEQ4W (-3.5 p<0.01) and ADA (-3.1 p=0.02) experienced significant reduction in SP-N at W16; all IXE tx pts had further reductions at W52. When inflammation was controlled per MRI+CRP, IXEQ4W (-3.8 p=0.2) and ADA (-3.1 p=0.4) had reduction in SP-N at W16 vs PBO (-2.4); all IXE groups had further improvements at W52. When inflammation was not controlled as measured by MRI+CRP, IXEQ4W (-3.7 p<0.001) had significant reduction in SP-N vs PBO (-1.7), whereas improvement with ADA (-2.6 p=0.06) was not significant; all IXE tx pts had further reduction by W52. For SF-36 bodily pain, improvements were observed with IXE and ADA at W16 and W52, whether inflammation was controlled or not controlled per MRI, CRP, MRI+CRP, or BASDAI 5/6. Conclusion This analysis adds support to the hypothesis that IXE improves pain in pts with and without measurable inflammation. Disclosure N. Maney: None. K. de Vlam: Consultancies; Celgene, Eli Lilly and Company, Galapagos NV, Novartis, Pfizer, and UCB Pharma. Grants/research support; Celgene. P.G. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma. P.J. Mease: Member of speakers’ bureau; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. P. Rahman: Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. V. Krishnan: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. D. Marcelino Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. S. Park: Shareholder/stock ownership; Eli Lilly and Company. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. W. Maksymowych: Grants/research support; AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Galapagos NV, Janssen, Novartis, Pfizer, and UCB Pharma; and is the Chief Medical Officer of CARE Arthritis Ltd.
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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 | 0.001 | 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".