The MESILICO study evaluated the long-term effect of mepolizumab (anti-IL-5) on airway structural remodeling in severe eosinophilic asthma over 3 years, using bronchoscopic airway sampling to measure sub-basement membrane thickness, airway smooth muscle area/thickness, epithelial damage, tissue eosinophils, Muc-5AC, E-cadherin, and FOXP3+ regulatory-like cells.
After 3 years, 25 bronchoscopy sub-study patients showed significant sustained reductions from baseline in sub-basement membrane thickness, airway smooth muscle area and layer thickness, epithelial damage, and tissue eosinophil numbers (all p<0.001), with additional improvements in Muc-5AC, E-cadherin histoscores, and FOXP3+ regulatory-like cells; 35/47 patients completing 3 years also had significant improvements in lung function, biomarkers, and reduced exacerbations (p<0.05).
Small sample size (only 25 of 41 bronchoscopy sub-study participants completed the 3-year bronchoscopy); no control arm, making it difficult to attribute structural changes solely to mepolizumab; significant dropout from the original cohort (47 enrolled, 35 completed 3 years) may introduce selection bias toward responders.
Sustained IL-5 blockade with mepolizumab over 3 years may produce meaningful structural airway improvements in severe eosinophilic asthma beyond symptom control, raising the possibility of disease modification — clinicians should consider long-term biologic continuation in well-responding patients.
