Adverse events during cystic fibrosis transmembrane conductance regulator modulator therapy in children with cystic fibrosis: an observational study.

BACKGROUND

Cystic fibrosis (CF) is a life-limiting genetic disease caused by pathogenic variants in the CFTR gene. CFTR modulators (CFTRms) have substantially improved clinical outcomes, but real-world data on symptoms reported during therapy in pediatric populations remain limited. This study evaluated the frequency and distribution of adverse events (AEs) reported during 12 months of CFTR modulator (CFTRm) therapy in pediatric and adolescent patients with CF.

METHODS

This prospective, dual-center observational study conducted in Poland included 74 patients aged 2-18 years receiving lumacaftor/ivacaftor (LI), tezacaftor/ivacaftor (TI), or elexacaftor/tezacaftor/ivacaftor (ETI). Reported symptoms were monitored prospectively and categorized as respiratory, nervous system, gastrointestinal, or other AEs. AE profiles according to patient characteristics and CFTRm regimen were explored.

RESULTS

At least one adverse event (AE) was reported by 90.5% of patients during follow-up. AE involving the respiratory and nervous systems were the most frequently reported, occurring in 79.7% and 75.7% of patients, respectively. Most AEs were intermittent and rarely required treatment interruption (n = 3). Lung function and nutritional status improved significantly during therapy. The overall frequency of reported AEs did not differ depending on the FEV1 or BMI outcomes. Nervous system AEs were more frequently reported among patients aged > 10 years and among patients receiving ETI compared with LI.

CONCLUSIONS

CFTRm therapy was generally well tolerated in this pediatric CF cohort. Reported AEs were common but predominantly intermittent and rarely led to treatment interruption. Systematic monitoring remains important, particularly for neurological symptoms, to better characterize tolerability of CFTRm therapy.