The rise of precision medicine in chronic obstructive pulmonary disease (COPD) has focused attention on identifying phenotypes, endotypes and treatable traits. T2 inflammation, often marked by eosinophilia, is associated with increased exacerbation risk, affecting up to 40% of COPD patients.1 Dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor alpha subunit, inhibits IL-4 and IL-13 pathways, modulating the T2 inflammatory cascade. Clinical trials like BOREAS and NOTUS have highlighted Dupilumab's efficacy in reducing exacerbations and improving lung function. However, its real-world applicability remains uncertain due to incomplete understanding of T2 inflammation's role in COPD pathogenesis.2 This study aimed to assess Dupilumab's real-world impact on exacerbation frequency in COPD.

COPD diagnosis followed GOLD guidelines.3 Patients included had at least 10 pack-year smoking history, persistent non-variable airflow obstruction, negative bronchodilator response, and no asthma history. Patients with at least three severe exacerbations in the prior year enrolled in the “Fragile COPD” program, which emphasized close monitoring, treatment optimization and targeting treatable traits. Exacerbations were classified as moderate (requiring systemic steroids and/or antibiotics) or severe (necessitating hospitalization). Patients with persistent exacerbations despite 12 months of optimized care and peripheral eosinophilia (>300cells/μL) were eligible for Dupilumab under compassionate use. After the initial supervised dose, all subsequent doses were self-administered. Eosinophilia was monitored quarterly, and lung function reassessed 9–12 months after initiating treatment.

Five patients were included, as detailed in Table 1. All were classified as COPD GOLD 3E and were on triple inhaled therapy (moderate-dose inhaled corticosteroids, long-acting beta-agonists, and long-acting muscarinic antagonists) using a single device. None had a history of childhood asthma; one had atopic dermatitis, while the others lacked type 2 inflammation comorbidities. Peripheral blood eosinophilia remained controlled during Dupilumab treatment, except for one patient who had transient elevation to 1900cells/μL. One corticosteroid-dependent patient, tapered prednisone from 40mg to 5mg daily after Dupilumab treatment. No severe adverse effects occurred. Adherence was good, except for one patient who voluntarily discontinued treatment for two months before resuming.

This real-life case series demonstrates that Dupilumab reduced exacerbation frequency and improved lung function in COPD patients with frequent exacerbations despite optimized therapy. Peripheral eosinophilia is the primary marker of T2 inflammation, though systemic steroid dependence and frequent exacerbations despite optimal treatment may also indicate this phenotype.4 These findings underscore the importance of identifying treatable traits, aligning with GOLD 2025 guidelines.3 In COPD patients with uncontrolled comorbidities (like atopic dermatitis), appropriate biologics can help maintain stability. Interestingly, the absence of significant Dupilumab-associated eosinophilia (>2000cells/μL), contrasts with findings in asthma.5

Dupilumab appears to be a safe and promising treatment for selected patients with COPD with frequent exacerbations and elevated eosinophil counts despite optimized therapy and well-managed treatable traits. It may effectively reduce exacerbation frequency, improve lung function and symptoms, and present minimal adverse effects. These findings align with prior clinical trials, including real-world evidence from BOREAS and NOTUS, reinforcing its protentional role in managing this challenging patient's population.