S174 Reduction of exacerbations according to type 2 inflammatory biomarkers with dupilumab treatment in patients with chronic obstructive pulmonary disease
Bibliographic record
Abstract
Purpose In BOREAS and NOTUS, add-on dupilumab reduced moderate-or-severe exacerbation rates and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. This post hoc analysis explored the predictive value of baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) for response to dupilumab treatment in patients with COPD and type 2 inflammation. Methods BOREAS (NCT03930732) and NOTUS (NCT04456673), Phase 3, randomized, placebo-controlled trials, enrolled 1874 patients (aged 40–85) COPD with moderate-to-severe airflow obstruction, and type 2 inflammation (screening blood eosinophil count ≥300 cells/mL) on triple inhalation therapy. Patients received dupilumab 300 mg every two weeks (q2w) or placebo for 52 weeks. Treatment rate ratios of dupilumab vs placebo and adjusted annualized moderate-or-severe exacerbation rates over a range of type 2 biomarkers were evaluated. Results The treatment rate ratio for moderate-or-severe exacerbations was 0.70 (95% confidence interval [CI]:0.61–0.81), 0.71 (0.61–0.83), 0.71 (0.61–0.83), and 0.72 (0.61–0.83) for patients with baseline blood eosinophil counts of 300, 500, 700, or 900 cells/µL, respectively (continuous biomarker-by-treatment interaction P=0.09). Reductions in exacerbation rates were observed over a range of baseline blood eosinophil counts (dupilumab: 0.57 [95% CI:0.51–0.63] for 300 cells/mL to 0.58 [0.51–0.65] for 900 cells/mL]; placebo: 0.81 [0.73–0.89] for 300 cells/mL to 0.81 [0.73–0.89] for 900 cells/mL). Furthermore, the treatment rate ratio for moderate-or-severe exacerbations was 0.69 (95% CI:0.59–0.80) and 0.67 (0.53–0.85) for patients with baseline immunoglobulin E (IgE) levels 100 IU/mL and 1000 IU/mL, respectively (continuous biomarker-by-treatment interaction P=0.83); reductions in exacerbation rates were observed regardless of baseline IgE levels (dupilumab: 0.56 [95% CI:0.50–0.63] for 100 IU/mL to 0.53 [0.44–0.63] for 1000 IU/mL; placebo: 0.82 [0.74–0.90] for 100 IU/mL to 0.78 [0.67–0.92] for 1000 IU/mL). Reductions in treatment rate ratio for exacerbations were also observed with increasing baseline FeNO levels from 0.69 (95% CI:0.60–0.80) for 20 parts per billion (ppb) to 0.56 (0.46–0.69) for 40 ppb (continuous biomarker-by-treatment interaction P=0.006), indicating a significant predictive value. Conclusion Dupilumab vs placebo reduced exacerbations independently of baseline blood eosinophil counts and IgE. Higher baseline FeNO levels were associated with a greater exacerbation reduction with dupilumab treatment compared with placebo.
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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 | 0.004 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.004 |
| 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) | 0.007 | 0.001 |
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".