Dupilumab after sequential omalizumab and benralizumab failure in T2-high asthma-COPD overlap: A case report.

Asthma-COPD overlap (ACO) remains therapeutically challenging, and evidence for biologic selection is limited due to the under-representation of overlap phenotypes in trials. We report a T2-high ACO patient who did not benefit from omalizumab or benralizumab but improved with dupilumab. This presents the case of a 67-year-old man with a long-term smoking history, atopy (elevated total IgE with polysensitization), eosinophilia, persistent airflow limitation, and frequent exacerbations despite optimized inhaled triple therapy. Sequential biologics included anti-IgE (omalizumab) and anti-IL-5Rα (benralizumab), with no meaningful reduction in exacerbations or improvement in lung function. After initiating dupilumab at a dose of 300 mg every 2 weeks, the patient reported a rapid improvement in symptoms, with no further exacerbations observed during the follow-up period. Pulmonary function showed a notable increase, with postbronchodilator FEV1 rising from 61 to 72% of the predicted value, and FEV1/FVC ratio improving from 69 to 84.5%. Asthma control scores increased from 12 to 20 by Week 12. Oral corticosteroid therapy was successfully discontinued, and no adverse events requiring discontinuation of dupilumab were recorded. In T2-high ACO unresponsive to anti-IgE and anti-IL-5Rα therapies, IL-4/IL-13 pathway inhibition with dupilumab may deliver a clinically meaningful benefit. Controlled studies are warranted to define its role in overlap phenotypes.