Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a CFTR modulator therapy approved for people with cystic fibrosis (pwCF) who have at least one phe508del mutation. However, its approval in the European Union (EU) for pwCF with non-phe508del mutations is lacking, because data on treatment response in this subgroup are scarce. Methods: This retrospective observational study evaluated six pwCF (ages 6 to 66) with responsive CFTR mutations (M1101K, R347P, 2789+5G>A, G551D) undergoing off-label ETI therapy. Evaluations were conducted at 0, 3, 6, 9, and 12 months, assessing lung function (FEV1), sweat chloride levels, body mass index (BMI), quality of life, medication satisfaction, ear, nose and throat (ENT) symptoms, and physical activity. A control group of four pwCF with classic symptoms and no ETI treatment was included. Results: FEV1 improved significantly after 3 and 6 months (p < 0.05) and stabilized by 12 months. Sweat chloride levels decreased significantly, with four pwCF achieving levels <60 mmol/L. Improvements in the upper and lower airway symptoms, medication satisfaction, and increased BMI were noted. Conclusions: ETI demonstrates high efficacy in this small group of pwCF with rare CFTR mutations, offering a treatment option that warrants further monitoring and evaluation.
Keywords: cystic fibrosis; elexacaftor/tezacaftor/ivacaftor; non-phe508del CFTR mutations; off-label use; rare CFTR mutations.