Weight gain is associated with reduced inflammation in children with cystic fibrosis on elexacaftor/tezacaftor/ivacaftor.

BACKGROUND

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators, notably Elexacaftor/Tezacaftor/Ivacaftor (ETI), have dramatically improved health of people with cystic fibrosis (CF). The mechanisms underlying ETI-associated weight gain remain unclear, but may include reduced energy expenditure, improved digestion and absorption, and/or increased caloric intake. We aimed to investigate factors associated with weight gain in children with CF treated with ETI.

METHODS

This prospective cohort study included patients from three Swiss centres with CF aged 6-17 years receiving ETI. We collected data before (M0), 7-14 days (D7/14) and 3-monthly up to 12 months (M12) after ETI initiation, including body mass index (BMI), systemic and intestinal inflammatory parameters, faecal elastase, sweat chloride, spirometry, lung clearance index, and caloric intake. Linear regression was performed to identify factors associated with BMI Z-score changes.

RESULTS

Among 59 patients (median (IQR) age 12 (9; 14) years, 51% girls, 76% without prior CFTR modulator treatment), BMI Z-score increased significantly from M0 (median (IQR): -0.4 (-1.0; 0.1)) to all subsequent visits (D7/14: -0.3 (-0.7; 0.2), p < 0.000; M12: -0.2 (-0.8; 0.3), p < 0.002). On multivariate analysis, increase in BMI Z-score was correlated with decrease in leucocyte count from M0 to D7/14 (p = 0.02) and with decrease in leucocyte count (p = 0.01) and faecal calprotectin (p = 0.02) from M0 to M12.

CONCLUSION

We report a significant increase in BMI and weight Z-scores as early as 10 days after ETI initiation. Our findings suggest that both early and long-term BMI increase following ETI initiation in children with CF is associated with a reduction in both systemic and intestinal inflammation.