Systemic immunologic effects of long-term dupilumab treatment in severe eosinophilic asthma beyond clinical outcomes

Introduction Dupilumab, an IL-4R α antagonist that blocks IL-4/IL-13 signalling, is used in severe eosinophilic asthma to improve clinical control and suppress type 2 inflammation. Methods We evaluated the clinical and systemic immunologic effects of dupilumab, focusing on type 2 biomarkers, total and aeroallergen-specific IgE, and FcεRI (High affinity IgE receptor) - expressing cells. Thirty-three adults with severe eosinophilic asthma were enrolled and followed up for 12 months in two Slovenian centres. Clinical assessments, spirometry, FeNO (Fractional exhaled nitric oxide), ACT (Asthma Control Test) scores, complete blood counts, total IgE, aeroallergen-specific IgE, and FcεRI expression on basophils were measured at baseline and at 1.5, 3, 6, and 12 months. Results Twenty-seven patients completed follow-up and were included in the final analysis. Dupilumab treatment resulted in significant improvement in ACT ( p = 0.0221), FEV1 ( p = 0.0139) and reduction in exacerbations requiring OCS (oral corticosteroid) ( p < 0.0001). FeNO declined by 78 %, total IgE by 83%, and aeroallergen-specific IgE by 65% with consistent reductions across perennial and seasonal allergens. Circulating eosinophils increased transiently, whereas basophils increased by 39%. Conclusions Dupilumab demonstrated sustained clinical improvement in patients with severe eosinophilic asthma, accompanied by broad immunologic modulation. Concurrent reductions in FeNO, total IgE, and aeroallergen-specific IgE indicate upstream inhibition of IL-4/IL-13-mediated inflammation, suggesting modulation of the underlying type 2 inflammatory network.