P276 Ixekizumab shows a pattern of pain improvement in patients with and without measurable inflammation in psoriatic arthritis
Bibliographic record
Abstract
Abstract Background/Aims The efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with psoriatic arthritis (PsA) has been previously reported using ACR 50 and Psoriasis Area and Severity Index (PASI) 100 responses. To minimize confounding effects, in this analysis we assessed the efficacy of either IXE or ADA monotherapy on reduction of pain beyond measurable inflammation in patients with active PsA and low C-reactive protein (CRP) (<5mg/L) at baseline. Methods SPIRIT-H2H (NCT03151551) was a 52 week (W), multicenter, randomized, open-label, parallel-group, assessor-blinded study evaluating the efficacy and safety of IXE vs ADA. Participants were randomized (1:1) to approved-label dosing of IXE or ADA. This post-hoc analysis included only patients treated with IXE or ADA as monotherapy and with low CRP (<5mg/L) at baseline. Changes in joint pain were measured using PsA Patient’s Assessment of Pain Visual Analog Scale (VAS). We stratified patients into four categories by two measures of inflammation: 1. Sustained low inflammation either by a. CRP<5 mg/L during W4-24 or b. ≥50% improvement in swollen joint count (SJC) during W8-24. 2. Fluctuating inflammation either by a. CRP≥5 mg/L at least once between W4-24 or < 50% improvement in SJC at least once between W8-24. Results 95 monotherapy patients with a CRP <5mg/L at baseline were included in this analysis. Baseline characteristics were similar between both treatment arms. In patients with fluctuating inflammation as measured by CRP, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients at W16 (IXE: -31.64, ADA: -25.33) that was sustained up to W52 (IXE: -47.69, ADA: -20.67). There was significance in favor of IXE at W32 (p = 0.0045) and W52 (p = 0.0288). In patients with sustained low inflammation as measured by CRP, there was comparable improvement in joint pain between IXE and ADA-treated patients. In patients with sustained improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W4 (IXE: -17.47, ADA: -10.42) that was sustained through W52 (IXE: -43.16, ADA: -32.62). In patients with fluctuating improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W16 (IXE: -22.00, ADA: -19.31) that was sustained through W52 (IXE: -28.57, ADA: -13.27). Conclusion This analysis suggests a different pattern of pain improvement in patients with low baseline CRP treated with IXE or ADA monotherapy, with a favorable pain reduction outcome for IXE-treated patients, even when inflammation is fluctuating as measured by CRP or SJC improvement. This analysis supports the hypothesis that IXE improves joint pain in PsA patients 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. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. P. Mease: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, GlaxoSmithKline. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB Pharma. Grants/research support; Janssen, Merck Sharp & Dohme, Neumentum, Novartis, Pfizer, Sun Pharma, and UCB Pharma. P. Rahman: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and UCB Pharma. 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. D. Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. C. Lin: Shareholder/stock ownership; Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. P. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma.
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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 | 0.002 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".