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

Abstract

IL-5 is a key mediator of severe eosinophilic asthma (SEA) and also may contribute to airway remodeling. Can mepolizumab, an anti-IL-5 antibody, modify airway remodelling in adult patients with SEA? 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. 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). In addition to its antiinflammatory effects, mepolizumab also may attenuate structural airway changes in SEA, which could contribute to its clinical benefits. ClinicalTrials.gov; No.: NCT03797404; URL: www. gov.