B107-16 Long-term Impact of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients With ≥1 F508del Mutation: Results From Four Years of Real-world Data

Abstract Background Elexacaftor/tezacaftor/ivacaftor (ETI) therapy provides substantial and sustained clinical benefits for people with cystic fibrosis (pwCF) carrying at least one F508del allele. This study evaluated the long-term impact of ETI on pulmonary function, nutritional status, pulmonary exacerbations, sweat chloride concentration, quality of life, and selected laboratory parameters over a 48-month follow-up period. Methods In this single-center, observational cohort study conducted at University Medicine Essen, Ruhrlandklinik, 106 pwCF with at least one F508del allele receiving ETI were followed for 48 months. Serial assessments included lung function, body mass index (BMI), pulmonary exacerbations, sweat chloride concentration, quality of life (CFQ-R), and laboratory parameters (HbA1c, liver enzymes, total bilirubin, and immunoglobulin G ). Statistical analyses were performed using SPSS Statistics version 31. Data normality was assessed by the Shapiro-Wilk test, and paired t-tests were used for within-subject comparisons. Results Among 106 participants (mean age 39 ± 12 years; 51% homozygous for F508del; 52.8% male), ETI therapy led to sustained clinical and biochemical improvements over 48 months. Mean ppFEV1 increased by 0.5 L (95% CI 0.39-0.62; p 0.001), corresponding to an increase in percent predicted FEV1 (ppFEV1) of 15.8% (95% CI 4.67-6.08; p 0.01 and inspiratory vital capacity by 1.06 L (95% CI 0.64-2.6; p 0.01). BMI rose by 0.64 kg/m² (95% CI 0.55-4.27; p 0.0001), while pulmonary exacerbations decreased by 28.9% (p 0.001). CFQ-R total scores improved by 46.7 points (95% CI 20.3-32.6; p 0.001). HbA1c decreased by 2.31% (95% CI 2.3-4.62; p 0.001), total bilirubin increased modestly by 0.93 µmol/L (95% CI 0.06-0.12; p 0.001), GOT decreased by 7.2 U/L (95% CI 6.2-15.5; p 0.001), and GPT by 5.5 U/L (95% CI 1.3-10.0; p = 0.006). IgG levels declined by 5.79 g/L (95% CI 2.83-10.1; p 0.001). Conclusion Consistent with previous randomized clinical trials, these findings confirm that ETI is an effective long-term treatment for individuals with cystic fibrosis carrying at least one F508del allele. While earlier studies primarily focused on selected clinical endpoints, our results extend this evidence by demonstrating ETI’s impact on laboratory parameters, including HbA1c, liver function tests, and immunoglobulin G. Collectively, these data underscore the therapeutic significance of ETI, highlighting durable and comprehensive improvements across multiple clinical and biochemical domains in this patient population. This abstract is funded by: None