Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least One F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.

OBJECTIVE: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers. STUDY DESIGN: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period. RESULTS: Among 608 patients on ETI, 109 (17.9%) reported at least 1 AE. The majority (n = 85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA P value .026). CONCLUSIONS: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.

Gestational and neonatal characteristics of children with cystic fibrosis: a cohort study.

OBJECTIVE: To examine whether the birth weight (BW) and the risks of being pre-term, low birth weight (LBW), and small for gestational age (SGA) of children with cystic fibrosis (CF) are different from nonaffected children. STUDY DESIGN: Retrospective cohort study. We examined all the children with CF born in Tuscany, Italy, from 1991 to 2002 (n = 70) comparing them to the entire population of non-CF-affected children born in the same period (n = 290,059). RESULTS: The mean BW of newborns with CF was 246.2 g lower than the mean BW of the non-CF neonatal population (P = .0003). Children with CF had a higher risk of being born pre-term (RR 2.62, P = .001), LBW (RR 2.66, P = .0009), and SGA (RR = 1.74, P = .04) than the non-CF-affected children. The mean BW of term newborns with CF was 205.7 g lower than that of term non-CF-affected babies (P = .0002). CONCLUSIONS: Our data show an association between CF and reduced BW and show a greater risk of being pre-term for babies with CF.