Real-World Dupilumab in Type 2 Chronic Obstructive Pulmonary Disease (COPD): A Single-Centre Compassionate-Use Case...

Background: Dupilumab, a monoclonal antibody blocking IL-4Rα, has recently demonstrated efficacy in patients with type 2 (T2)-inflamed chronic obstructive pulmonary disease (COPD) in the BOREAS and NOTUS trials. Real-world experience in older patients with predominant chronic bronchitis phenotype remains limited. Methods: We report a single-centre case series of 12 consecutive patients with T2-inflamed COPD treated with dupilumab 300 mg every two weeks under a compassionate-use programme at San Carlo di Nancy Hospital, Rome (first administration: April 2025). Eligibility required ≥2 moderate or ≥1 severe exacerbation in the prior 12 months despite triple inhaled therapy and a blood eosinophil count ≥300 cells/µL. Follow-up ranged from 3 to 12 months, with 6 months pre-specified as the primary analysis timepoint; data at 9 and 12 months are reported as descriptive observations. Endpoints included paired changes in annualised exacerbation rate (AER), CAT score and item-level CAT, and FEV₁, with exploratory univariate Spearman analyses of candidate baseline predictors of response. Results: The cohort was elderly (mean age 73.6 ± 5.2 years, range 65-82), predominantly female (8/12, 67%) and characterised by a chronic bronchitis phenotype with high symptom burden (mean baseline CAT 22.8 ± 7.5; CAT item 2 [phlegm] median 3, IQR 3-4). Severe exacerbations decreased significantly (Wilcoxon p = 0.0156; mean AER 0.75 → 0.19 events/patient-year; 6/12 improved, 0/12 worsened). The mean cumulative function showed a standardised incidence ratio of 0.46 (95% CI 0.19-0.95; p = 0.033) versus the pre-dupilumab rate. Mean FEV₁ increased by +66 mL at 1 month (n = 11, paired Wilcoxon p = 0.025), +78 mL at 3 months (n = 10, p = 0.082) and +120 mL at 6 months (n = 10, p = 0.007). Total CAT decreased from 22.9 to 12.5 at 6 months (Friedman p = 0.0007), with the largest absolute reductions in item 2 (phlegm; Δ = -2.6 at 6 months, p < 0.001) and item 3 (chest tightness; Δ = -2.5 at 6 months, p = 0.002). Higher baseline CAT was associated with greater reduction in severe AER (Spearman ρ = -0.79, p = 0.002). Conclusions: In this elderly real-world cohort with phlegm-driven T2 COPD, dupilumab was associated with a significant decrease in severe exacerbations, a clinically meaningful gain in lung function and a marked improvement in mucus-related symptoms. Further studies are warranted to confirm these findings and to clarify whether the reduction in severe exacerbations translates into a measurable mortality benefit.