Biomarker-Associated Remission After Switching to Dupilumab in Severe Asthma Following Failure of Prior Biologics

<b>Background/Objectives</b>: Severe asthma remains difficult to treat, even with the range of biologics we now have that target type 2 inflammation. Some patients do not respond well enough to the first biologic they try, which raises the question of whether switching to another option can help. In this study, we looked at how patients who had unsatisfactory therapeutic outcomes on other biologics responded-both clinically and at the biomarker level-after switching to dupilumab. <b>Methods</b>: We reviewed data from the Allergy and Clinical Immunology Unit of Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, between January and June 2025. The study included fifteen adults with uncontrolled severe asthma who had previously been treated for at least six months with benralizumab, omalizumab, or mepolizumab before switching to dupilumab. We evaluated demographic, clinical and laboratory data. Lung function (Forced Expiratory Volume in 1 s (FEV₁)), blood eosinophils, total and specific IgE to staphylococcal enterotoxins, eosinophil cationic protein (ECP), free light chains (FLC), and FeNO were assessed at the time of the switch and again after 12 months. Comparisons were made using paired tests, and a <i>p</i>-value < 0.05 was considered statistically significant. <b>Results</b>: After a year on dupilumab, we saw clear improvements: mean FEV₁ went up by about 10.8% predicted (<i>p</i> = 0.002), FeNO dropped by an average of 22 ppb (<i>p</i> = 0.005), blood eosinophils fell by roughly 400 cells/µL (<i>p</i> = 0.003), and ECP levels decreased by 13 µg/L (<i>p</i> = 0.009). Kappa FLCs also showed a significant drop (<i>p</i> = 0.04). Clinically, 40% of patients met criteria for a meaningful response, and 20% achieved complete remission. Dependence on oral corticosteroids was notably reduced. Baseline levels of eosinophils, ECP, IgE, and FLCs correlated with response to treatment. <b>Conclusions</b>: Our study, despite the small sample size, highlights that in patients with severe asthma who do not show a good response to their first biologic, switching to dupilumab can lead to significant improvements. Markers of type 2 inflammation at baseline might help predict who benefits most. Larger, multi-center, prospective studies are needed to confirm these results.