Purpose: We investigated the efficacy of Mepolizumab treatment by assessing airway remodeling outcomes and patient characteristics associated with treatment response. Methods: MESILICO is a multicenter study. Patients with late-onset severe eosinophilic asthma and fixed obstruction were eligible to be administered Mepolizumab. Forty-seven patients were recruited. Bronchial biopsies were obtained before treatment initiation and after 12 months of treatment. Airway remodeling was assessed via changes from baseline in endobronchial biopsy basement membrane thickness, airway smooth muscles mass, epithelial integrity and tissue eosinophil number. Clinical parameters such as spirometry values (FEV1, FVC, PEF) were also evaluated. This trial is registered with ClinicalTrials.gov, number NCT04612556. Results: Preliminary results from sixteen patients are presented. Treatment with mepolizumab resulted in a significant reduction from baseline to 12 months of treatment in basement membrane thickness (p=0.007), airway smooth muscle area (p=0.011), extent of epithelial damage (p=0.009), and tissue eosinophil numbers (p=0.030). Significant improvements were also found in respiratory parameters (FEV1-p=0.036, FVC-p=0.008). Patients with more than 10% FEV1 improvement were found with less damaged epithelium after 12 months of treatment (p<0.001). Also, increased PEF values were positively correlated with high percentages of damage epithelial reduction (p=0.001, r=0.787). Conclusions: In our study, 12 months of mepolizumab treatment improves airway remodeling which is consistent with disease modification by mepolizumab. Funding:GSK214163.