Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in 6 to 11-Year-Olds with Cystic Fibrosis.

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) provided substantial health benefits to children with cystic fibrosis (CF) in clinical trials; there is less information about its effectiveness in a "real world" setting. Methods: The pediatric PROMISE substudy enrolled CF children 6 to <12 years of age starting ETI. Outcomes measured at baseline (pre-ETI), 1, 3, 6 and 12 months after ETI initiation included the lung clearance index (LCI_2.5), % predicted forced expiratory volume in 1 second (ppFEV₁), the CFQ-R respiratory domain symptom score (CFQ-R RD), height, weight, oropharyngeal (OP) cultures, culture and DNA-based analysis of sputum microbiology (when sputum available). Sweat chloride was assessed at baseline, 1 and 6 months. Results: 125 participants were enrolled at 20 US CF centers. Lung function improvement post-ETI initiation was rapid and sustained through 12 months, with a mean decrease in LCI_2.5 of -0.79 (95% CI -1.04, - 0.55) and a mean increase in ppFEV₁ of 5.6 (95% CI 3.4, 7.7). Respiratory symptoms also improved significantly (mean change in CFQ-R RD of 4.1 (95% CI [1.94, 6.24]). Sweat chloride decreased significantly at 6 months (mean change -47.2 mmol/L (95% CI -51.99, -43.8)). Weight, BMI and height z scores were not different from baseline at 12 months. S. aureus prevalence in OP or sputum cultures did not change but its density in sputum cultures decreased a mean of 1.47 log₁₀ CFU/g (95% CI -2.37, -0.58) at 12 months. Conclusions: Initiation of ETI in a real-world setting was associated with clinically significant improvements in lung function and symptoms, and decreased S. aureus sputum density at one year; lung function improvements were smaller than those reported in clinical trials.