Exocrine Pancreatic Function in Pediatric Patients After Two Years of Triple CFTR Modulator Therapy: Is It Possible
C M López Cárdenes1,2,3, S Vicente Santamaría1,2,3, R García Romero4
1Unidad de Fibrosis Quística. Hospital Universitario Ramón y Cajal, Madrid, Spain.
Background:
Improvement in exocrine pancreatic function in people with Cystic fibrosis (PwCF) after ivacaftor and lumacaftor/ivacaftor has been documented. Data on triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) are limited.
Methods:
In this multicenter, prospective, observational study, we reviewed changes in fecal elastase-1 (FE-1) in the pediatric population with exocrine pancreatic insufficiency (EPI) after 2 years of ETI. Patients were classified according to FE-1: mild-moderate EPI as 100-199 μg/g and severe EPI as <100 μg/g. Demographic, clinical, anthropometric, and body composition data were collected. Body composition was measured using bioelectrical impedance analysis.
Results:
Fifty-three children were recruited (58.5% males). The median age was 12 years [IQR: 9.0-14.5], and 56.6% were homozygous for F508del. Values of FE-1 below fifteen were designated with a 0. At baseline, the median FE-1 was 0.00 [IQR: 0.00-0.00]. We observed a slight yet statistically significant improvement in FE-1 values 2 years after ETI (Wilcoxon test, p < 0.05). We classified patients into three groups based on FE-1 values. At baseline, 98% were in the severe EPI group (FE-1 < 100 μg/g), the remaining 2% were in the mild-moderate group (FE-1 100-199 μg/g). Two years after triple therapy, six (11.4%) children showed a change in FE-1 to at least 100 μg/g from the baseline. Three (5.7%) had a change in FE-1 ≥ 200 μg/g from baseline, and the other three (5.7%) had a change in FE-1 between 100 and 199 μg/g. A significant reduction in daily lipase intake was observed (6346 vs. 5703 L/kg/day; p < 0.05). BMI Z-score improved over 2 years (-0.55 vs. -0.38; p < 0.05). Body composition data were available for 27 patients, showing increased fat mass and fat-free mass after ETI therapy. No differences in body composition were found when stratified by EPI groups.
Conclusion:
CFTR modulators have improved pulmonary function and anthropometric measures in PwCF. Based on these findings, CFTR modulators may also enhance exocrine pancreatic function in pediatric patients.
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