Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence

Fibrosis transmembrane conductance regulator (CFTR) modulators (CFTRms) have significantly improved outcomes in people with cystic fibrosis (CF). Real-world evidence, particularly from national and international CF registries, is essential to assess their long-term effectiveness and safety. We reviewed published studies using registry data to evaluate the impact of CFTRms on clinical outcomes in individuals with CF. A narrative review of studies published between 2015 and 2025 was conducted, focusing on registry-based evaluations of ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor. Primary outcomes included lung function, pulmonary exacerbations, nutritional status, and survival. Fifty-seven registry-based studies confirmed the benefits of CFTRms across diverse CF populations. Ivacaftor has demonstrated sustained improvements in forced expiratory volume in one second (FEV1), reduced exacerbations, and improved nutritional outcomes. Lumacaftor/ivacaftor and tezacaftor/ivacaftor have shown modest benefits, especially in homozygous F508del patients. The introduction of elexacaftor/tezacaftor/ivacaftor has led to unprecedented improvements in lung function and quality of life, along with a reduced need for lung transplantation. Methodological heterogeneity and incomplete data remain challenges. Registry data provide essential, complementary evidence to clinical trials and support the effectiveness of CFTRms in routine care. Continued efforts are needed to harmonize registry methodologies and outcome measures.