Improved Clinical Outcomes With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease: Real-World Evidence From an Italian Single-Center Study
The combination therapy of Elexacaftor, Tezacaftor, and Ivacaftor (ETI) has led to notable improvements in lung function and overall clinical outcomes in individuals with cystic fibrosis—results that have not been achieved with earlier CFTR modulators. Despite these promising outcomes, limited data exist regarding the long-term use of ETI in adolescents and patients with advanced lung disease. Additionally, variability in therapeutic response may be influenced by genotype differences (homozygous versus heterozygous) and prior exposure to other CFTR modulators.
To address these gaps, a retrospective study was conducted to evaluate the impact of ETI on several key clinical parameters over a two-year period. The primary endpoints included changes in percent predicted forced expiratory volume in one second (ppFEV1), body mass index (BMI), and sweat chloride concentration (SwCl) measured at baseline and at 6, 12, and 24 months post-therapy initiation. Secondary outcomes assessed included the frequency of pulmonary exacerbations (PEx), Cystic Fibrosis Questionnaire-Revised (CFQ-R) scores, adverse events, and rates of mortality and lung transplantation.
A total of 139 patients were included and monitored for up to two years following ETI initiation. The data revealed significant improvements in ppFEV1 and BMI after 12 months of treatment, with an average increase of 16% in ppFEV1 (p < 0.001) and a gain of 1.5 kg/m² in BMI (p = 0.005). Although a slight decline in both values was observed after 24 months, the overall benefit was sustained. The reduction in SwCl from 84 to 37 mmol/L over the 24-month period (p < 0.001) further underscored the efficacy of ETI in correcting the underlying chloride transport defect. Notably, the response to therapy was independent of genotype but varied between patients who were treatment-naïve and those previously on other CFTR modulators. Additionally, the rate of pulmonary exacerbations decreased by 58.3% compared to pre-treatment levels. Overall, ETI was well tolerated with no discontinuations due to toxicity. Galicaftor Improvements were observed across lung function, sweat chloride levels, BMI, pulmonary exacerbation rates, and CFQ-R scores, reinforcing the long-term clinical benefit and safety of ETI therapy in a diverse cystic fibrosis population.