Mepolizumab Demonstrates Disease Stability Benefits Across COPD Severity Spectrum at ATS 2026
Key Insights
Pooled analysis of three Phase III trials shows mepolizumab added to triple therapy reduced exacerbations requiring emergency visits or hospitalization by 23% versus placebo in eosinophilic COPD (search) patients.
Disease stability at Week 52 was achieved in 18% of mepolizumab-treated patients versus 15% on placebo, with the greatest benefit seen in GOLD 4 severe disease (16% vs 6%).
AI-assisted CT analysis from the COPDGene cohort identified mucus plugging as a quantifiable biomarker independently associated with higher mortality and exacerbation risk.
The American Thoracic Society (ATS) International Conference 2026, held May 15–20 in Orlando, Florida, showcased a rapidly evolving landscape in chronic obstructive pulmonary disease (COPD (search)) care, with biologic therapies, AI-assisted phenotyping, and digital health tools taking center stage. Among the most clinically significant findings was a pooled analysis demonstrating that mepolizumab, an anti-IL-5 (search) monoclonal antibody, not only reduces exacerbations but may help patients achieve disease stability—an emerging therapeutic target in COPD management.
Mepolizumab and the Pursuit of Disease Stability
Building on the FDA approval of mepolizumab for eosinophilic COPD (search), Criner et al. presented a pooled analysis of the Phase III METREX, METREO, and MATINEE trials showing that mepolizumab added to inhaled triple therapy significantly reduced exacerbations requiring emergency department visits and/or hospitalizations by 23% versus placebo in patients with a blood eosinophil count above 150 cells/μL.
A complementary pooled analysis by Singh et al. extended this concept beyond exacerbation reduction, evaluating disease stability at Week 52 using a composite endpoint requiring no moderate or severe exacerbations, maintenance or improvement in COPD (search) Assessment Test (CAT) score, and preserved or improved lung function. Among 1,146 patients with blood eosinophil counts of at least 300 cells/μL and ongoing triple therapy, 18% of those receiving mepolizumab achieved disease stability compared with 15% of those receiving placebo.
The greatest contributor to this difference was a reduction in exacerbations: 52% of mepolizumab-treated patients met the exacerbation criterion for disease stability versus 42% with placebo. Notably, benefits were observed across all Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity categories. In patients with the most severe GOLD 4 disease, disease stability was achieved in 16% of patients receiving mepolizumab compared with just 6% of those receiving placebo.
"These findings support the use of blood eosinophils as a relevant biomarker for identifying patients with COPD (search) who may benefit from targeted anti-IL-5 (search) therapy," the investigators concluded, though they noted the analysis was conducted post hoc and requires further prospective validation.
Ensifentrine: A Non-Biologic Add-On Strategy
Beyond biologics, ensifentrine—a first-in-class dual phosphodiesterase (PDE)3/PDE4 (search) inhibitor with bronchodilator and anti-inflammatory effects—emerged as a practical add-on option. In the RELIEF study, an observational 6-month longitudinal analysis, most participants were already receiving stable triple therapy. Among patients with a baseline CAT score above 10, the mean CAT score improved from 24.6 at baseline to 20.3 at 1 month and 19.9 at 3 months, with 65% meeting the CAT responder threshold at both time points.
A separate real-world analysis of 2,372 patients receiving ensifentrine with concomitant dual or triple therapy showed an 11% reduction in annualized severe exacerbations and a 17% reduction in COPD (search) emergency room visits after treatment initiation. Investigators emphasized that longer-term data will be needed to better define its role in routine COPD management.
AI-Assisted CT Phenotyping Redefines Risk Stratification
ATS 2026 highlighted a parallel shift toward precision phenotyping, framing COPD (search) as a heterogeneous disease requiring more refined tools than spirometry alone. In the COPDGene cohort, an AI-based algorithm was used for automated detection of CT airway mucus plugs in 8,971 participants. Greater mucus plug burden was associated with lower post-bronchodilator forced expiratory volume in 1 second, increased air trapping, worse quality-of-life scores, reduced 6-minute walk distance, and an independently higher risk of mortality and exacerbations.
A complementary analysis from the SOURCE early COPD (search) progression cohort applied a deep learning pipeline to baseline CT scans from 657 younger participants with smoking history, identifying mucus plugs in 7% of participants. Although uncommon, mucus plugs were associated with emphysema, CT-defined functional small-airway disease, and more frequent exacerbations. These findings suggest that AI-assisted CT analysis may transform mucus plugging from a visually recognized imaging feature into a quantifiable biomarker with potential value for COPD phenotyping, risk stratification, and future phenotype-directed interventions.
Digital Tools for Earlier Detection and Monitoring
Accessible technologies also emerged as a promising strategy to support earlier COPD (search) detection. Wang et al. evaluated Cough Search, a multimodal AI-based cough analysis software, in a multicenter prospective study of 378 participants. The tool demonstrated 92% sensitivity and 89% specificity as a standalone diagnostic aid, and when combined with physician assessment, achieved 93% sensitivity and 94% specificity—showing higher sensitivity than portable spirometry-assisted physician diagnosis while maintaining non-inferior specificity.
A separate prospective study evaluated smartphone-based spirometry using machine learning, showing strong agreement with conventional spirometry for forced expiratory volume in 1 second/forced vital capacity, excellent twice-daily reproducibility, and the ability to capture diurnal variation and deviations from baseline.
Real-World Gaps in COPD (search) Care
Despite therapeutic advances, the conference underscored persistent implementation challenges. The US DUALITY disparities study, encompassing 338,947 patients with COPD (search) who had experienced one severe or two moderate exacerbations, found that only 6.9% initiated triple therapy within 12 months, with variation depending on age, sex, race/ethnicity, payer coverage, geography, and symptom profile.
A separate study focused on food insecurity in COPD (search) demonstrated that 34.5% of patients self-reported food and/or financial insecurity. Together, these findings suggest that future COPD care must extend beyond effective medication prescriptions to address implementation gaps and recognize social needs as part of routine care.
The COPD (search) updates presented at ATS 2026 reflect a field moving toward individualized, clinically practical care—matching personalized interventions with innovation to ensure they reach those most likely to benefit.