Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety
Bibliographic record
Abstract
Purpose: Randomized trials report that single-inhaler triple therapy is more effective than dual bronchodilators at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this effect may have been influenced by the forced withdrawal of inhaled corticosteroids (ICS) at randomization. We used an adaptive selection new-user design to compare single-inhaler triple therapy with dual bronchodilators in real-world clinical practice. Patients and Methods: We identified a cohort of COPD patients, 40 years or older, treated during 2017-2020, from the United Kingdom's Clinical Practice Research Datalink, a real-world practice setting. ICS-naïve patients initiating single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, after adjustment by propensity score weighting. Results: The cohort included 4106 new users of single-inhaler triple therapy and 29,702 of dual bronchodilators. Single-inhaler triple therapy was the first maintenance treatment in 44% of the users and 43% had no COPD exacerbations in the prior year. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with triple therapy relative to dual bronchodilators was 1.08 (95% confidence interval (CI): 1.00-1.16). Among patients with two or more prior exacerbations the HR was 0.83 (95% CI: 0.74-0.92), while for those with prior asthma diagnosis it was 0.86 (95% CI: 0.70-1.06) and with blood eosinophil count >300 cells/µL it was 0.89 (95% CI: 0.76-1.05). The incidence of severe pneumonia was increased with triple therapy (HR 1.50; 95% CI: 1.29-1.75). Conclusion: In a real-world setting of COPD treatment among ICS-naïve patients, thus unaffected by ICS withdrawal, single-inhaler triple therapy was not more effective than dual bronchodilators at reducing the incidence of exacerbation, except among patients with multiple exacerbations. Single-inhaler triple therapy should be initiated mainly in patients with multiple exacerbations while, for most others, dual bronchodilators are just as effective whilst avoiding the excess risk of severe pneumonias.
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How this classification was reachedexpand
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.001 | 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 teacher head, 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".