Green Light for Response: Clinical Stratification of Response to Biologic Therapy in Severe Asthma

Raquel Lopez-Rodríguez,1 José Antonio Cañas,2,3 Ignacio Mahíllo-Fernández,4,5 Manuel J Rial3,6 1Allergy Department, Hospital Universitario Lucus Augusti, Lugo, Spain; 2Immunology Department, Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid, Madrid, Spain; 3CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain; 4Department of Biostatistics and Epidemiology, Fundación Jiménez Díaz University Hospital, Madrid, Spain; 5Department of Medicine, Universidad Autónoma de Madrid, CIBERES, Instituto de salud Carlos III, Madrid, Spain; 6Allergy Department, Complexo Hospitalario Universitario de Ferrol, Ferrol, SpainCorrespondence: Raquel Lopez-Rodríguez, Allergy Department, Hospital Universitario Lucus Augusti, Dr. Ulises Romero, 1, Lugo (Lugo), 27003, Spain, Email [email protected]: Biologic therapies have transformed the management of severe asthma; however, treatment response remains heterogeneous and difficult to anticipate in routine practice. Conventional biomarkers alone have limited ability to identify patients who will achieve complete or sustained clinical benefit. This study aimed to explore baseline clinical and inflammatory thresholds associated with response to biologic therapy and to propose an exploratory, clinically oriented stratification framework.Methods: We conducted a secondary analysis of a real-world, single-center, ambispective cohort of adults with severe uncontrolled asthma treated with biologic therapies and followed for at least 12 months. Clinical response was assessed at 6 and 12 months using the multidimensional EXACTO and FEOS scales. Baseline clinical and biological variables were analyzed using exploratory ROC curve analyses to identify thresholds associated with complete clinical response.Results: Among 64 patients, the proportion of complete responders increased from 14% at 6 months to 32.1% at 12 months. No significant differences in response were observed between biologic agents. Higher baseline blood eosinophil counts and a history of frequent exacerbations were associated with improved outcomes. Exploratory eosinophil thresholds of approximately 440 and 435 cells/μL were identified at 6 and 12 months, respectively. Female sex and nasal polyposis were also associated with higher response rates. Based on these findings, three exploratory response profiles reflecting different likelihoods of response were identified.Conclusion: Baseline clinical and inflammatory characteristics may support response stratification in severe asthma. Given that maximal benefit may be achieved over longer treatment periods, extended follow-up should be considered before modifying biologic therapy. The proposed framework is exploratory and provides a basis for future prospective validation.Keywords: severe asthma, biological therapy, clinical thresholds, biomarkers, super-responders