Impact of Mepolizumab on Airway Remodeling and Inflammation in Severe Eosinophilic Asthma

BACKGROUND: IL-5 is a key mediator of severe eosinophilic asthma (SEA) and also may contribute to airway remodeling. RESEARCH QUESTION: Can mepolizumab, an anti-IL-5 antibody, modify airway remodelling in adult patients with SEA? STUDY DESIGN AND METHODS: Thirty-seven patients who were eligible for mepolizumab were included prospectively. Mepolizumab 100 mg was administered subcutaneously every 4 weeks for 12 months. Bronchial biopsies and bronchoalveolar lavage (BAL) were performed at baseline, 6 months, and 12 months. Clinical and functional outcomes, airway remodeling, and inflammatory markers were assessed at each time point. RESULTS: At 12 months, mepolizumab was shown to improve asthma control and FVC before bronchodilation and reduce the number of exacerbations, oral corticosteroid courses, and hospitalizations. These clinical and functional improvements were associated with a reduction in reticular basement membrane thickness (P < 0.0001), airway smooth muscle (ASM) mass (P = .0066), and proliferating cell nuclear antigen-positive ASM cells (P < .0001) in the bronchial mucosa at both 6 and 12 months. BAL fluid showed reduced levels of tenascin-C at 6 and 12 months and of fibulin-1 at 12 months. Blood eosinophil counts decreased significantly (P < .0001), and eosinophils were almost completely depleted in BAL fluid (P = .023) at 12 months. Submucosal eosinophilia was reduced to a lesser extent (P = .063). INTERPRETATION: In addition to its antiinflammatory effects, mepolizumab also may attenuate structural airway changes in SEA, which could contribute to its clinical benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03797404; URL: www. CLINICALTRIALS: gov.