Elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and rare mutations

• Published in: Pediatric pulmonology 2024-12, Vol.59 (12), p.3383-3390
• Main Authors: Fainardi, Valentina, Cresta, Federico, Sorio, Claudio, Melotti, Paola, Pesce, Emanuela, Deolmi, Michela, Longo, Francesco, Karina, Kleinfelder, Esposito, Susanna, Pisi, Giovanna
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aminophenols - therapeutic use; Benzodioxoles - therapeutic use; cell culture; Chloride Channel Agonists - therapeutic use; Compassionate Use Trials; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Drug Combinations; elexacaftor/tezacaftor/ivacaftor; ETI; Female; Humans; Indoles - therapeutic use; Male; modulator; Mutation; organoid; organoids; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Pyrrolidines - therapeutic use; Quinolones - therapeutic use; rare mutations; rare variants; theratyping; Treatment Outcome; Young Adult
• ISSN: 8755-6863; 1099-0496; 1099-0496
• DOI: 10.1002/ppul.27211

Introduction The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment. Methods In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short‐term cultures of nasal epithelium obtained from rectal suction biopsies and nasal brushing were obtained from four subjects. Results After 2 months of ETI, all patients (4 males, mean age 30.1 ± 13.3 years) showed a significant increase of FEV1% predicted values [+8.0 (3.5–12.7) %, p