Impact of elexacaftor-tezacaftor-ivacaftor (eti) on lung disease in patients with cystic fibrosis

SESSION TITLE: Genetic and Developmental Disorders Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2023 12:00 pm - 12:45 pm PURPOSE: Impact of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies, such as elexacaftor-tezacaftor-ivacaftor (ETI), on structural changes in the lungs in people with CF (pwCF) is unclear. Purpose of this study was to determine the impact of ETI on clinical parameters and on structural lung disease as measured by the changes in the chest CT scans in pwCF. METHODS: Percent predicted FEV1 (ppFEV1), body mass index (BMI) and microbiologic data were collected at initiation and at 3-month intervals for 1 year. Chest CT scans were completed before starting ETI therapy (baseline) and at one year on ETI therapy and were analyzed by two pulmonologists independently. RESULTS: Sample size was 67 pwCF, 30 (44.8%) males, median age of 25 (16, 33.5) years. Significant increases in ppFEV1 and BMI were observed by 3 months of ETI therapy with persistence of improvement throughout one year of ETI therapy (p<0.001 at all-time points for both). After one year on ETI, pwCF had significant reductions in Pseudomonas aeruginosa (-42%) and MRSA (-42%) positivity (p<0.01 for both). Chest CT comparisons: None of the pwCF had worsening of chest CT parameters during one year of ETI therapy. At baseline, chest CT scans revealed bronchiectasis in 65 (97%) pwCF and at one-year follow-up, it was absent in 4 (6%) and decreased in 7(11%). Bronchial wall thickening was noted in 64 (97%) and at one-year follow-up, it was absent in 5 (7.5%) and decreased in 53 (79%). Mucous plugging was noted in 63 (95.5%) and at one-year follow-up, it was absent in 11 (17%) and decreased in in 50 (77%). Hyperinflation/air trapping was noted in 44 (67%) and at one-year, it was decreased in 11 (18%) absent in 26 (43%) and unchanged in 24 (39%). When the presence or absence of bronchial wall thickening, bronchiectasis, hyperinflation, and mucous plugging were compared at baseline and after one year of ETI therapy, there were statistically significant differences in hyperinflation (p=0.041) and mucous plugging (p=0.023). In brief, improvement in bronchiectasis was noted only in few (17%) pwCF but improvement was more evident in other parameters on chest CT such as bronchial wall thickening (86%), mucous plugging (94%) and hyperinflation (61%). In significantly more pwCF, resolution of mucous plugging and hyperinflation was noted. It seems like CFTR modulator use leads to a decrease in mucous plugging, thus lessening peri-bronchial inflammation and bronchial obstruction. Its role in already established bronchiectasis is less clear; it is possible that it may impact early bronchiectasis, but that more advanced bronchiectasis with advance lung disease may become irreversible. CONCLUSIONS: ETI significantly improved clinical outcomes and structural lung disease in many pwCF as documented by improvement in chest CT scans. CLINICAL IMPLICATIONS: ETI significantly improved clinical outcomes and lung disease in many pwCF as documented by improvement in chest CT scans after ETI therapy. DISCLOSURES: No relevant relationships by Mariah Eisner No relevant relationships by Courtney Gushue No relevant relationships by Melissa Holtzlander No disclosure on file for Terri Johnson No disclosure on file for Karen McCoy No relevant relationships by Shahid Sheikh