Real-world experience with a generic formulation of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator protein. Since 2021, Argentina has provided a generic formulation of the triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). The aim of this study is to evaluate clinical effects on pulmonary function, nutritional status, sputum microbiology, sweat test (ST), respiratory exacerbations, and quality of life in patients using this generic formulation. METHODS: People with cystic fibrosis (PwCF), both sexes, aged ≥6 years, received the generic ETI formulation at Hospital de Pediatria Prof. Dr J.P. Garrahan. PRIMARY ENDPOINT: clinical variables were analyzed before and after one year of treatment. Secondary endpoint: pulmonary function was compared between groups with and without prior modulator therapy, both before and after treatment RESULTS: Fifty-five PwCF were included. The median age at ETI initiation was 11.6 years (IQR 8.9-14.5). Thirty-one (56.36%) had not previously received modulators. Baseline median ppFEV1 of the entire cohort was 80.7 (IQR 62.7-91), and after one year, ppFEV1 increased to101 (IQR 88.5-105.75). Median BMI z-score improved from -0.32 (IQR -0.77 to 0.35) to -0.09 (IQR -0.67 to 0.43) after one year. The median reduction in ST was 45 mEq/L. Pulmonary exacerbations showed significant decline. Pseudomonas aeruginosa decreased in sputum cultures, whereas the Burkholderia cepacia complex remained unchanged. Quality of life improved. No severe adverse effects were reported. After 12 months, lung function improved significantly in the group without previous modulator treatment. CONCLUSIONS: As previously reported for the original ETI formulation, the Argentine generic formulation showed similar results for clinical variables.