Genotype-dependent biochemical response to elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis: A 24-month real-world study - 19/05/26
Abstract |
Background |
Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) care; however, its efficacy in pediatric subjects carrying one ETI-responsive and one non-responsive CFTR variant remains incompletely characterized. This study compared the real-world response to ETI using sweat chloride concentration (SCC) as a key biomarker of CFTR function.
Methods |
In this retrospective, single-center study, pediatric subjects aged 6–18 years, carrying at least one p.Phe508del variant and on ETI, were included. Participants were stratified by genotype into those with two responsive variants and those with one responsive variant. SCC, percent predicted FEV1 (ppFEV1), BMI z-score, and pulmonary exacerbations were assessed at baseline (T0), 3–6 months (T1), 12 months (T2), and 24 months (T3). Longitudinal analyses were performed using mixed-effects models.
Results |
Among 80 pediatric participants, those with two responsive variants had significantly lower median SCC at all follow-up time points (T1: 31.0 vs 46.0 mmol/L; T2: 26.0 vs 41.0 mmol/L; T3: 32.0 vs 45.0 mmol/L; all p < 0.01) and were more likely to achieve SCC <30 mmol/L. Regression models confirmed that carrying two responsive variants was independently associated with a 30% lower SCC (coefficient −0.36, 95% CI −0.53 to −0.18) and a 95% reduction in odds of elevated SCC (OR 0.05). No significant differences were observed in ppFEV1, BMI z-score, or pulmonary exacerbation rates.
Conclusion |
Children and adolescents with CF carrying two ETI-responsive variants exhibit a superior biochemical response to ETI. The absence of differences in clinical outcomes likely reflects preserved baseline status, reinforcing SCC as a sensitive biomarker of CFTR modulation in pediatric subjects. These findings support the use of SCC as a sensitive early biomarker of CFTR correction, particularly in pediatric patients with preserved clinical status.
Le texte complet de cet article est disponible en PDF.Highlights |
• | This single-center study provides 24-month real-world evidence of a genotype-dependent Elexacaftor/tezacaftor/ivacaftor (ETI) response. |
• | Children with two ETI-responsive CFTR variants achieve a greater reduction in sweat chloride than those with only one ETI-responsive variant. |
• | Sweat chloride emerges as a sensitive biomarker of CFTR correction in children with preserved lung function. |
• | Cystic fibrosis genotypes should be a key consideration in forecasting treatment response, especially under expanded eligibility criteria. |
Keywords : Cystic fibrosis, CFTR modulators, Sweat chloride, Treatment outcome, Children
Plan
Vol 257
Article 108853- juin 2026 Retour au numéro
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