Abstract
Clinical trials demonstrate the short-term efficacy of dual CFTR modulators, but long-term real-world data is limited. We aimed to investigate the effects of 24-month lumacaftor/ivacaftor (LUM/IVA) therapy in pediatric CF patients (pwCF). This observational study included pwCF homozygous for F508del mutation treated between 2021 and 2023. We report data for the first 24 months from therapy initiation. Variables were analyzed separately for ages 2-5, 6-11, and over 12. Data from 49 pwCF (median age: 9.3 years (5.5-14.2)) showed that ppFEV1 values after a transient increase at 12 months, decreased from 102% (82-114) at baseline to 87% (74-96) at 24 months. The decrease was more pronounced with higher initial ppFEV1. Median sweat chloride concentration decreased from 75 mmol/L (69-82) to 57 mmol/L (43-70) without any association with respiratory function change. Median BMI z-score increased from - 0.81 (- 1.37-0.49) to - 0.39 (- 0.88 to - 0.04) (p = 0.288), and the proportion of underweight and overweight children decreased. Skeletal muscle mass remained stable, while fat mass significantly increased (p = 0.011). Fecal elastase levels improved, especially among younger patients. These findings underscore the potential benefits of early initiation of CFTR modulator therapy in pediatric CF patients, highlighting improvements in nutritional status and pancreatic function.