This study aimed to investigate the impact of Elexacaftor/Tezacaftor/Ivacaftor (ETI) on key clinical outcomes in patients with Cystic Fibrosis (CF), with a particular focus on lung function, Body Mass Index (BMI), Sweat Test (ST) results, and mental health parameters such as depression and anxiety. The rationale behind this investigation stemmed from the need to better understand not only the physical benefits of ETI therapy but also its potential effects on psychological well-being.

An observational, prospective, multicentre study was conducted involving 108 adult patients who initiated ETI therapy between December 2019 and December 2023. These patients underwent regular clinical, functional, and microbiological evaluations, and they were asked to complete standardized questionnaires assessing quality of life, anxiety, and depression throughout the follow-up period. The study specifically sought to determine whether there were changes in anxiety and depression levels over time as patients received ETI treatment.

After 12 months of treatment, the results showed significant improvements in several clinical outcomes. Patients experienced notable increases in BMI, enhanced lung function as measured by FEV1%, improved sweat test results, and overall better quality of life scores on the CFQ-R. Despite these marked physical health benefits, the levels of anxiety and depression did not show significant changes during the study period. However, when the data were stratified, younger patients (under 28 years old) and those with homozygous Phe508del mutations exhibited significantly higher levels of anxiety, although depression levels remained largely unchanged across these subgroups. Additionally, a moderate correlation between anxiety and depression was observed, which appeared to strengthen as the treatment progressed.

In conclusion, while ETI treatment significantly enhances lung function, BMI, sweat test outcomes, and overall quality of life in CF patients, its impact on mental health appears more complex. The overall levels of anxiety and depression did not show significant change over time in the general patient population. However, certain subgroups, particularly younger patients and those with the homozygous Phe508del mutation, experienced elevated anxiety levels. These findings suggest that although ETI provides substantial physical health benefits, attention to mental health, especially in vulnerable subgroups, remains crucial in the comprehensive management of CF. Galicaftor