Real-World Clinical Outcomes of Lumacaftor-Ivacaftor or Tezacaftor-Ivacaftor Therapy in Children With Cystic Fibrosis Homozygous for Phe508del.

BACKGROUND

Cystic fibrosis (CF) is a progressive, life-shortening disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR modulator therapies targeting the common Phe508del mutation have been introduced in clinical practice. This study evaluates the real-world effects of 1 year of dual CFTR modulator therapy - lumacaftor/ivacaftor or tezacaftor/ivacaftor - in children homozygous for Phe508del.

METHODS

A retrospective single-center (Belgium) study was conducted in children with CF aged 2-18 years who initiated dual modulator therapy. Clinical data from 1 year before and after treatment initiation were analyzed. Outcomes included changes in sweat chloride concentration (SCC), lung function (percent predicted forced expiratory volume in 1 s (ppFEV1)), frequency of exacerbations and hospitalizations, sputum microbiology, nutritional status (body mass index (BMI) z-score), liver function, vitamin levels, and ophthalmologic status.

RESULTS

Fifty-four children (mean age 8.5 years) were included. After 1 year, SCC decreased significantly with a mean of 14 mmol/L (p < 0.001). Lung function showed a modest improvement with a mean increase of 2.3% in ppFEV1 (range: +16% to -15%, p = 0.023). No significant changes were observed in exacerbation or hospitalization rates, nor in sputum microbiology. Nutritional status and liver function remained stable, though vitamin A levels increased significantly. The therapy was generally well-tolerated.

CONCLUSION

This real-world study demonstrates that dual CFTR modulators in children homozygous for Phe508del result in a significant reduction in SCC and modest improvements in ppFEV1. These findings support the efficacy and safety of dual modulator therapy in pediatric CF care.