Factors associated with sustained Pseudomonas aeruginosa infection following elexacaftor/tezacaftor/ivacaftor treatment: Real-world data from the European cystic fibrosis society patient registry

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) therapy reduces airway infection rates with Pseudomonas aeruginosa (PsA). This study assessed factors associated with sustained chronic PsA infection and evaluated clinical outcomes after one year of ETI, stratified by PsA status. Methods: Using the European Cystic Fibrosis Society Patient Registry (ECFSPR), we identified people with cystic fibrosis (pwCF) who initiated ETI between 2019 and 2022. Multivariable logistic regression was used to identify clinical and demographic predictors of persistent chronic PsA. Changes in clinical outcomes from one year before to one year after ETI were analyzed using semiparametric models. Results: Among 8188 pwCF with chronic PsA prior to ETI, 4908 (59.9 %) remained chronically infected after one year, while 3280 (40.1 %) transitioned to non-chronic PsA. Older age (OR 1.63, 95 %CI: 1.49–1.78) and lower baseline ppFEV₁ (OR 0.64, 95 %CI: 0.58–0.70) were the strongest predictors of persistent chronic PsA. The improvement in ppFEV₁ was similar between those who remained chronic (12.5 %, 95 %CI: 11.8–13.3) and those who shifted to non-chronic status (13.0 %, 95 %CI: 12.2–13.8; p = 0.074). BMI z-score improvements did not differ significantly between groups (p = 0.086). However, the mean hospital admission days was lower in those who shifted to non-chronic PsA (1.2 vs. 1.9 days; p < 0.001). Conclusion: Risk factors for sustained PsA infection post-ETI are associated with older age and lower ppFEV1. Nonetheless, improvements in lung function and nutritional status were comparable, regardless of PsA status. Further research is required to better understand how PsA affects CF lung disease in the era of ETI treatment.