Continuous glucose monitoring to track metabolic changes in youths with cystic fibrosis before and after initiation of elexacaftor/tezacaftor/ivacaftor therapy.

INTRODUCTION: Glucose tolerance abnormalities can be detected in preschool and school-age children with cystic fibrosis. There is limited data on the impact of CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) on their trajectories. We examined CGM metrics before and after ETI initiation across different pediatric age groups. METHODS: We included participants from the French MODUL-CF real world study aged 2-18 years with at least 24 hours of CGM data before initiation of ETI and a 2nd CGM 12±3 months following ETI start. The cohort was stratified in 3 groups based on the age at ETI initiation: <6, 6-12 and >12 years. CGM derived glucose metrics were compared before and after ETI. RESULTS: 98 patients with CF were enrolled, including 13 preschool children, 55 school age children and 32 adolescents. At baseline, participants displayed a time in tight glucose range (TITR) of 89.8%(84.1, 93.4) with 34% of the whole cohort spending >10% of time>140mg/dL (TA140). Following treatment, TITR increased of ∼2%(+1.8[-1.8, +6.0]%) (p=0.004). This was associated with a 0.4% reduction of mild-hyperglycemia (>140mg/dL) and a lower CV (21.5%(19.0, 24.7) vs 19.6%(17.0, 22.6), p<0.001). Those with TA140≤10% at baseline displayed greater weight gain and improvement of lung function respect to the group with TA140>10%. CONCLUSION: ETI is associated with improvement of CGM glucose in children and adolescents with CF. TA140 before ETI initiation may impact the trajectory of clinically relevant outcomes.