The Proof of the Pudding Is in the Eating: Real-Life Intra- and Extrapulmonary Impact of Elexacaftor/Tezacaftor/Ivacaftor

Abstract

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) has shown significant improvements in pulmonary and nutritional status in persons with cystic fibrosis (pwCF). Less is known about the extrapulmonary impact of ETI and effects on airway microbiology, lung clearance index (LCI), and fraction of exhaled nitric oxide (FeNO).

Methods: This is a multicenter prospective observational trial, including 79 pwCF ≥18 years eligible for ETI. Assessments were done at the initiation of and 3 and 6 months into treatment with ETI. Outcomes included forced expiratory volume in 1 s (FEV1), LCI, FeNO, sputum or cough swab culture, body mass index (BMI), cystic fibrosis questionnaire-revised respiratory domain (CFQ-R RD), sinonasal outcome test-22 (SNOT-22), general anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9), fecal elastase-1 (FE-1), adherence to baseline therapies, exacerbation rate, and adverse events.

Results: Our cohort included 79 pwCF (31 ± 11(SD) years) with a baseline ppFEV1 of 68 ± 23. Forty-two (53%) pwCF were previously treated with a CFTR modulator. In the entire study group, there were significant improvements from baseline in ppFEV1, LCI, FeNO, annualized exacerbation rate, BMI, CFQ-R RD, and SNOT-22 (p < 0.05 for all). Airway culture positivity for methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa also decreased during the study period. There was no significant change in FE-1, GAD-7, or PHQ-9. Adherence to dornase alfa and hypertonic saline decreased.

Conclusion: ETI treatment led to significant improvements in respiratory and nutritional status, alongside a decrease in adherence to chronic supportive therapies. We did not observe any significant changes in exocrine pancreas function or in questionnaire scores for depression and anxiety.

Keywords: CFTR modulator; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Extrapulmonary impact; Real life.