Effectiveness of Mepolizumab on Mucus Plug Reduction and Clinical Outcomes in Severe Eosinophilic Asthma: A Prospective Observational Study

Background: Mucus plugs are common in severe eosinophilic asthma and contribute to airway obstruction. Interleukin (IL)-13 drives goblet cell hyperplasia and mucus overproduction, and IL-5 activates eosinophils, increasing mucus viscosity. Mepolizumab, an anti-IL-5 monoclonal antibody, reduces eosinophilic inflammation, but its effect on mucus plugs is unclear. Objective: To evaluate the effectiveness of mepolizumab in reducing mucus plugs and their association with biomarkers and clinical outcomes. Methods: This prospective study included 47 severe eosinophilic asthma patients treated with mepolizumab for 12 months. High-resolution computed tomography was used to quantify mucus plugs using the Mucus Plug Score (MPS, range 0–20). Demographic and clinical data were collected at baseline and after 12 months. Correlations between MPS and clinical variables were assessed. The most commonly used definitions of clinical remission were also evaluated. Results: Mepolizumab significantly reduced MPS from 4 (3–7) to 1 (0–2) (P < 0.0001) after 12 months of treatment. At baseline, patients with high MPS (≥4) had higher blood eosinophil counts and sputum eosinophils, more frequent exacerbations, and worse lung function. Reductions in MPS were significantly correlated with decreases in blood eosinophil counts (r = 0.40; P = .0488), sputum eosinophils (r = 0.58; P = .0376), and OCS dose (r = 0.38; P = .0372), and with increases in FEV₁% (r = –0.37; P = .0425). Clinical remission was more frequent in patients with lower MPS (0-3), although this difference was not statistically significant. Conclusions: Mepolizumab effectively reduces mucus plug burden and is associated with improvements in inflammatory biomarkers and clinical outcomes. These results support mucus plugs as a promising imaging biomarker in severe eosinophilic asthma, warranting confirmation in larger, controlled studies.