Dupilumab-induced eosinophilia in severe asthma: 2-year follow-up real-life evidence from biologic-naïve and previously treated patients

Data from real-life settings regarding dupilumab-associated eosinophilia remains limited, particularly concerning potential risk factors for developing hypereosinophilia after treatment initiation. METHODS: We conducted a prospective observational study including an initial cohort of 36 patients with severe asthma treated with dupilumab and followed for up to two years. Blood eosinophil count (BEC), asthma outcomes, and treatment response - including ACT score, lung function, exacerbations, oral corticosteroid use, and the EXACTO scale as a multidimensional response measure - were assessed at baseline and at weeks 24, 52, and 104. Eosinophilia was categorized as mild (>500 cells/μL), moderate (>1500 cells/μL), or severe (>5000 cells/μL), and hypereosinophilia as moderate-severe eosinophilia. RESULTS: Transient eosinophilia occurred in 47.2% of patients and transient hypereosinophilia in 19.4%, with most cases being asymptomatic. Two patients (5.6%) developed a clinical presentation suggestive of eosinophilic granulomatosis with polyangiitis (EGPA). Hypereosinophilia was more frequent among patients who had switched from prior anti-IL-5/IL-5R therapy. Among the cases that developed hypereosinophilia, 42.9% persisted at the 2-year follow-up, whereas mild eosinophilia persisted in 65% of patients. Nevertheless, dupilumab treatment resulted in significant improvements in asthma control and treatment response outcomes, irrespective of eosinophil levels or prior biologic exposure. CONCLUSION: Eosinophilia is a common finding in patients receiving dupilumab, generally without significant safety implications. The use of dupilumab is safe and highly effective, even in patients previously treated with anti-IL-5/IL-5R biologics. However, rare cases of severe eosinophilic complications may occur, making long-term systematic monitoring advisable.