Real-World Evaluation of Outcomes and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Pediatric Patients With Cystic Fibrosis: A Retrospective Study

Abstract

Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy has significantly improved clinical outcomes in people with cystic fibrosis (PwCF) carrying at least one Phe508del CFTR mutation. However, real-world evidence on the safety and effectiveness of ETI in pediatric populations remains limited, particularly in children with more severe disease phenotypes who are often excluded from clinical trials. We analyzed clinical, functional, and microbiological data from pediatric CF patients aged 6-17 years treated with ETI between October 2022 and March 2024. Lung function (ppFEV₁, ppFVC), nutritional status (BMI, BMI z-score), sweat chloride concentration (SwCl), quality of life (CFQ-R), pulmonary exacerbations (PEx), and airway pathogens were assessed at baseline and after 6-12 months. Adverse events (AEs) and therapy discontinuations were also recorded. Twenty-four patients (n = 10 aged 6-11 years; n = 14 aged 12-17 years) were included. At 12 months, mean ppFEV₁ increased by 15% (p = 0.013), BMI by 2.4 kg/m² (p = 0.16), BMI weight z-score by 0.33 (p = 0.63), and height z-score by -0.33 (p = 0.72), SwCl decreased by 46 mmol/L (p < 0.001), and CFQ-R respiratory domain improved by 14 points (p < 0.001). PEx rates decreased by 27.6% after 12 months. Reductions in airway pathogen prevalence, particularly Staphylococcus aureus and Pseudomonas aeruginosa, were observed. AEs occurred in 14.8% (n = 4) of patients, were mild-to-moderate, and resolved with dose reduction. ETI therapy was associated with marked improvements in lung function, nutritional status, and quality of life, along with reductions in PEx and airway pathogens, in a real-world pediatric CF cohort. These findings support ETI use in this population, with careful AE monitoring and dose adjustment when needed.

Keywords: cystic fibrosis; effectiveness; elexacaftor‐tezacaftor‐ivacaftor; pediatric setting; safety.

FIGURE 1

Prevalence of the most common chronic infections in pediatric CF patients (6–17 years). The line chart illustrates the percentage of colonization by specific pathogens (culture positivity for H. influenzae , S. aureus , mucoid and rugose P. aeruginosa , and K. pneumoniae ) over various time intervals relative to ETI. The x‐axis represents the time intervals, ranging from 12 months before ETI to 12 months after ETI, while the y‐axis indicates the percentage of positive bacterial cultures. The chart tracks colonization trends for H. influenzae , mucoid and rugose forms of P. aeruginosa , K. pneumoniae , and S. aureus . Distinct patterns of colonization are observed, with a general decline in percentages following ETI.

FIGURE 2

Pathogen culture positivity pre‐ and post‐ETI by age group. Tripanel dumbbell plots show the number of positive respiratory cultures for each pathogen before initiation of elexacaftor/tezacaftor/ivacaftor (ETI; blue circles) and after treatment (red open squares). Panel A: all patients (n = 27); Panel B: age 6–11 years (n = 10); Panel C: age 12–17 years (n = 17). Horizontal lines connect paired pre–post values; numbers on the right indicate absolute changes (Δ). Two‐sided p values are shown adjacent to the connectors (*p < 0.05). Significant reductions are observed for Staphylococcus aureus , rugose and mucoid Pseudomonas aeruginosa , and Klebsiella pneumoniae .

FIGURE 3

Longitudinal variation of clinical and auxological parameters. Panels show (A) variation of ppFEV₁ across time points, (B) variation of BMI across time points, (C) variation of weight‐for‐age z‐score by age group (6–11 years and 12–17 years), and (D) variation of height‐for‐age z‐score by age group (6–11 years and 12–17 years). Data are presented as box plots (median, interquartile range, and overall range). Assessments were performed at baseline (T0), 6 months (T6), and 12 months (T12). A significant improvement was observed for ppFEV₁ (panel A), with p < 0.05 for the comparison between T0 and T12. No statistically significant differences were detected for BMI, weight‐for‐age z‐score, or height‐for‐age z‐score (panels B–D).