Biomarker-Associated Remission with Anti-IL-4R/IL-13 Therapy After Failure of Prior Biologics in Severe Asthma

Background/Objectives 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. Methods We reviewed data from the Allergy and Clinical Immunology Unit of Fondazione Policlinico Universitario A. Gemelli-IRCCS 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 assessed lung function (FEV₁), blood eosinophils, IgE, eosinophil cationic protein (ECP), free light chains (FLC), and FeNO at the time of the switch and again after 12 months. Statistical comparisons were made using paired tests, with significance set at p 0.05. Results After a year on dupilumab, we saw clear improvements: mean FEV₁ went up by about 10.8% predicted (p = 0.002), FeNO dropped by an average of 22 ppb (p = 0.005), blood eosinophils fell by roughly 400 cells/µL (p = 0.003), and ECP levels decreased by 13 µg/L (p = 0.009). Kappa FLCs also showed a significant drop (p = 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. Conclusions For patients with severe asthma who do not show a good response to their first biologic, switching to dupilumab can lead to significant clinical and biomarker improvements. Markers of type 2 inflammation at baseline might help predict who benefits most. Larger, prospective studies are needed to confirm these results.