Impact of Elexacaftor-Tezacaftor-Ivacaftor on lung disease in cystic fibrosis

Background: In people with cystic fibrosis (pwCF), the impact of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, such as Elexacaftor-Tezacaftor-Ivacaftor (ETI), on structural changes in the lungs is unclear.

Objective: To determine the impact of ETI on clinical parameters and on structural lung disease as measured by the changes in the chest computed tomography (CT) scans in pwCF.

Methods: Percent predicted forced expiratory volume in one second (ppFEV1), body mass index (BMI), and microbiologic data were collected at initiation and 3-month intervals for 1 year. Chest CT scans before starting ETI therapy (baseline) and at 1-year on ETI therapy were compared by two pulmonologists independently.

Results: The sample size was 67 pwCF, 30 (44.8%) males, median age of 25 (16, 33.5) years. Significant increases in ppFEV1 and BMI observed by 3 months of ETI therapy persisted throughout 1 year of ETI therapy (p < 0.001 at all-time points for both). After 1 year on ETI, pwCF had significant reductions in Pseudomonas aeruginosa (-42%) and MRSA (-42%) positivity. None of the pwCF had worsening of chest CT parameters during 1 year of ETI therapy. Comparing chest CT findings at baseline and at 1-year follow-up, bronchiectasis was present in 65 (97%) pwCF and at 1-year follow-up decreased in 7 (11%). Bronchial wall thickening 64 (97%), decreased in 53 (79%). Mucous plugging in 63 (96%), absent in 11 (17%), and decreased in 50 (77%). Hyperinflation/air trapping in 44 (67%), decreased in 11 (18%), absent in 27 (44%) CONCLUSIONS: ETI significantly improved clinical outcomes and lung disease as documented by improvement in chest CT scans.