Mepolizumab Reduces the Risk of Severe Exacerbations and Healthcare Resource Utilization in Chronic Obstructive Pulmonary Disease: Results from the MATINEE Phase III Randomized Controlled Trial
Bibliographic record
Abstract
Abstract Rationale: Patients with chronic obstructive pulmonary disease (COPD) and raised blood eosinophil counts (BEC) experience more frequent and severe exacerbations, which can lead to increased healthcare resource utilization (HCRU) and mortality. Mepolizumab is a humanized monoclonal antibody specifically targeting interleukin-5, a central cytokine in type 2 inflammation. Methods: The MATINEE (NCT04133909) Phase III, randomized, double-blind, parallel-group trial enrolled patients with COPD, BEC ≥300 cells/µL at screening, and a history of exacerbations despite receiving optimal inhaled triple therapy (dual long-acting bronchodilators plus inhaled corticosteroid [fluticasone propionate ≥500 μg/day or equivalent]). Patients ≥40 years of age were randomized 1:1 to mepolizumab 100 mg administered subcutaneously every 4 weeks for 52-104 weeks versus placebo, in addition to optimal inhaled triple therapy. This secondary analysis reports the time to first severe exacerbation (requiring hospitalization ≥24 hours or resulting in death) and to first exacerbation leading to emergency department (ED) visit and/or hospitalization, alongside the annualized rates and proportions of patients experiencing ≥1 of such exacerbations, and post hoc patient-reported HCRU, all up to Week 104. Results: Overall, 804 patients were randomized and treated (403 mepolizumab/401 placebo). Numerically lower proportions of mepolizumab-treated patients versus placebo experienced ≥1 severe exacerbation (11% vs 15%) and ≥1 exacerbation requiring ED visit and/or hospitalization (14% vs 18%; Table) by Week 104. With mepolizumab, compared with placebo, the annualized rate of severe exacerbations was 34% lower, alongside a 35% lower rate in exacerbations requiring ED visit and/or hospitalization (rate ratio [95% confidence interval (CI)] 0.66 [0.43, 1.01] and 0.65 [0.43, 0.96], respectively). The risk of experiencing a first severe exacerbation over 104 weeks was 26% lower with mepolizumab versus placebo (hazard ratio [95% CI]: 0.74 [0.50, 1.08]), alongside a 27% lower risk of a first exacerbation leading to ED visit and/or hospitalization (0.73 [0.51, 1.04]). Patient-reported HCRU resulting from exacerbations by Week 104 was similar in mepolizumab- and placebo-treated patients, as illustrated by the number of exacerbations requiring ED visits (11% vs 15%), urgent care/outpatient clinic visits (6% vs 6%), general ward admissions (12% vs 12%), and intensive care admissions (5% vs 4%). Mepolizumab-treated patients experienced lower mean resource utilization per exacerbation in ED visits, urgent care/outpatient clinic visits, and days in intensive care (Table). Conclusions: Mepolizumab as add-on treatment to optimal triple therapy may help prevent severe exacerbations and reduce subsequent healthcare burden in patients with COPD, 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 | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".