Clinical Outcomes in Patients with Cystic Fibrosis Receiving CFTR Modulators: A Comparison of Childhood Versus Adolescent Initiation

TL;DR

Starting CFTR modulator therapy in childhood leads to better clinical outcomes and fewer hospitalizations compared to starting in adolescence for cystic fibrosis patients.

Contribution

This study provides evidence that early initiation of CFTR modulator therapy in children improves clinical outcomes compared to initiation in adolescents.

Findings

Adolescents had higher rates of respiratory failure and infections compared to children.

Adolescents had higher hospitalization rates and longer hospital stays.

Mortality rates were similar between the two age groups.

Abstract

Background/objectives: Cystic fibrosis (CF) is a life-limiting genetic disorder affecting multiple organ systems. This study compared clinical outcomes, hospitalization rates, and survival between children and adolescents with CF who received CFTR modulator therapies (ivacaftor, lumacaftor, tezacaftor, and elexacaftor). Methods: A retrospective cohort study was conducted using data from the TriNetX global collaborative network. Patients with CF aged 2–12 years (children) and 13–18 years (adolescents) who received CFTR modulator therapies were included. The propensity score matching balanced baseline characteristics between the two age groups. Results: After propensity score matching, 946 patients per group were analyzed. The incidence of respiratory failure (3.81% vs. 1.06%, p < 0.001) and respiratory infections (62.7% vs. 57.5%, p = 0.021) were significantly higher in adolescents compared to children. Adolescents had a higher risk of respiratory failure (HR = 3.6, 95% CI = 1.79–7.21, p < 0.001) and respiratory infections (HR = 1.09, 95% CI = 1.01–1.17, p < 0.001). Adolescents also had a higher hospitalization rate (29.6% vs. 20.3%, p < 0.001), with a 47% higher risk (HR = 1.47, 95% CI = 1.22–1.77, p = 0.001), more hospital visits per person (8.8 vs. 3.7, p = 0.004), and longer hospital stays (32.7 vs. 20.4 days, p = 0.006). Mortality rates were similar between the groups (1.58% vs. 1.26%, p = 0.56). Conclusions: CF patients who initiated CFTR modulator therapies during adolescence had a higher incidence of respiratory failure, respiratory infections, hospitalization rates, and healthcare resource utilization compared to those who started therapy in childhood, despite similar mortality rates. These findings highlight the importance of the early initiation of CFTR modulator therapies.

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