INHALED ANTI-IGE: IGE COMPLEXES AS A MUTATION-AGNOSTIC BIOLOGIC THERAPY FOR CYSTIC FIBROSIS WITH RARE MUTATIONS

Cystic fibrosis (CF) is a progressive, multisystem disorder caused by mutations in the CFTR gene, leading to thickened airway mucus, persistent inflammation, and chronic infection. Although CFTR modulators have revolutionized care, 10–15% of patients with rare or splicing mutations are ineligible for these therapies and remain at high risk for pulmonary complications, allergic bronchopulmonary aspergillosis (ABPA), steroid dependence, and cystic fibrosis-related diabetes (CFRD). This review explores the emerging use of preformed anti-IgE:IgE complexes delivered as a biologic aerosol. This approach targets the CD23 pathway to suppress IgE-mediated and type 2 inflammation, reduce corticosteroid exposure, and protect lung and pancreatic function. This article discusses key considerations for formulation, aerosol engineering, and delivery, along with a proposed treatment model and anticipated outcomes for this vulnerable population. By addressing unmet needs in mutation-ineligible CF patients, inhaled anti-IgE:IgE therapy represents a promising mutation-agnostic strategy to improve clinical and immunological outcomes.