Real-World Response to Dupilumab as Add-on Therapy in Adults and Adolescents with Type 2 Severe Asthma: A Spanish Cohort Study

Background: Dupilumab has demonstrated efficacy in type 2 severe asthma in clinical trials. Real-world data, particularly from Spain and including patients with prior biologic failure, remains limited. This study evaluated the effectiveness and safety of dupilumab in a Spanish cohort with type 2 severe asthma over 12 months. Methods: Retrospective, multicenter observational study in adult and adolescent patients (≥ 12 years) with type 2 severe asthma treated with dupilumab for at least six months. Clinical data, including exacerbations, lung function (FEV 1 ), Asthma Control Test (ACT), quality of life (Mini-AQLQ), systemic corticosteroid use, and biomarkers (total IgE, eosinophil count, FeNO), were collected at baseline, 6, and 12 months. The EXACTO scale was used to assess response in non-oral corticosteroid (OCS)-dependent patients at 12 months. Subgroup analyses included chronic rhinosinusitis with nasal polyps (CRSwNP) and OCS-dependent patients at baseline. Results: A total of 156 patients were included; 54.5% had received prior biologic therapies. Significant improvements (p< 0.005) from baseline to 12 months were observed in exacerbations (1.43 to 0.20 per year), FEV 1 (2530.10 to 2824.59 mL), ACT (15.84 to 21.31), and Mini-AQLQ (27.24 to 74.27). Total IgE and FeNO significantly decreased whereas blood eosinophilia increased. In non-OCS-dependent patients (n=78), 56.4% were good or super-responders according to the EXACTO scale. CRSwNP patients (n=66) significantly improved in asthma and nasal symptoms. Among OCS-dependent patients (n=35), 68.6% discontinued OCS by 6 months. Comparable clinical improvements in exacerbation rates, lung function and overall response were observed in biologic-naïve and biologic-pretreated patients, consistent with similar EXACTO scores (4.92 ± 1.29 vs. 4.55 ± 1.37, respectively; p =0.166). No new safety signals were identified. Conclusion: This Spanish real-world study confirms sustained effectiveness and acceptable safety of dupilumab in type 2 severe asthma, including patients with prior biologic failure and comorbid CRSwNP, supporting its use in routine clinical practice. Plain Language Summary: Asthma is a long-term disease that makes it hard to breathe because of inflammation and narrowing of the airways. People with type 2 severe asthma often have frequent symptoms and exacerbations despite using standard treatments, and some rely on daily oral corticosteroids (OCS) to control their disease. Dupilumab is a newer medication that targets specific inflammatory pathways linked to this type of asthma. While it has proven effective in clinical studies, less is known in real-world settings, particularly in Spain. This study reviewed the medical records of 156 adults and adolescents with type 2 severe asthma who were treated with dupilumab for at least six months at multiple centers in Spain. Researchers assessed asthma exacerbations, lung function, symptom control, quality of life, use of OCS, and blood markers over 12 months. After one year of treatment, patients experienced far fewer asthma exacerbations, better lung function, and improved quality of life and asthma control scores. Many patients were able to stop taking daily OCS. Those with asthma and nasal polyps also reported significant relief in their breathing and nasal symptoms. No new safety issues appeared. These findings confirm that dupilumab works well and is safe for people with type 2 severe asthma, including those who did not respond to other biologic treatments. The results support using dupilumab in everyday clinical practice to help patients gain better control of their asthma. Keywords: dupilumab, exacerbations, lung function, quality of life, real-world evidence, severe asthma, Spain, type 2 inflammation