Effectiveness of Mepolizumab and Dupilumab in Patients with Asthma-COPD Overlap (ACO) compared to Severe Uncontrolled Asthma: A Retrospective Observational Cohort Study.

BACKGROUND The coexistence of asthma and chronic obstructive pulmonary disease (COPD), known as asthma-COPD overlap (ACO), presents unique diagnostic and therapeutic challenges. Although biological therapies such as Mepolizumab and Dupilumab have transformed the management of severe eosinophilic asthma, their role in ACO remains poorly defined due to the exclusion of this phenotype from most clinical trials.

METHODS This retrospective observational study aimed to evaluate the real-world effectiveness of Mepolizumab and Dupilumab in patients with ACO compared to those with severe uncontrolled asthma (SUA). We included 212 patients treated in a specialized asthma unit between 2017 and 2024, all with at least 12 months of follow-up. Treatment response was assessed using clinical tools (EXACTO scale and SEPAR-REMAS criteria).

RESULTS Among Mepolizumab-treated patients (ACO n = 10; SUA n = 132), those with ACO had significantly lower baseline FEV1 and lower rates of good/complete response (14.2% vs. 60%, p < 0.03) and clinical remission (0% vs. 20.9%). In the Dupilumab group (ACO n = 10; SUA n = 60), ACO patients showed lower baseline ACT scores and FEV1, with reduced response rates (25% vs. 55%) and no clinical remission, although differences were not statistically significant. Despite limited power due to small ACO sample sizes, the magnitude of these differences suggests a clinically relevant reduction in biologic effectiveness in ACO.

CONCLUSION These findings emphasize the urgent need for dedicated studies in ACO, a population with a high disease burden and limited treatment guidance. Individualized therapeutic approaches should be prioritized until robust clinical trial data becomes available.