Background: The pulmonary benefits of elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis (CF) are well-documented across available literature while the extrapulmonary benefits are less well-known. The purpose of this research study was to evaluate endpoints that characterize the extrapulmonary benefits of elexacaftor/tezacaftor/ivacaftor therapy to better understand the full benefits and help elucidate factors that may contribute to choice of therapy.
Methods: A retrospective chart review of CF patients with active orders for elexacaftor/tezacaftor/ivacaftor was completed between October 1, 2019 and December 31, 2021 for growth metric data (height, weight, body mass index (BMI) and associated z-scores) and pancreatic enzyme dosing at baseline (0), 3, 6, and 12 months. Patients ≥ 6 years of age with at least two data points (baseline and one follow-up) were included in the study. Charts were reviewed for hospitalization and antibiotic use two years prior to elexacaftor/tezacaftor/ivacaftor approval and two years after approval in patients ≥ 12 years of age. The primary objectives were to determine whether there was an increase in BMI z-score after initiation of elexacaftor/tezacaftor/ivacaftor at 3 and 6 months. Paired t-tests (or Wilcoxon signed rank where appropriate) were used to assess change in baseline to 3-, 6-, and 12-month endpoints and change from baseline to the study period for hospital admission and antibiotic courses.
Results: A total of 33 patients were included in the study. The median patient age was 11.0 years old (IQR: 9.0-16.0). The mean difference in BMI z-score between baseline and 3 months was 0.1 (95% CI: 0.0, 0.2; p = 0.0456) and 6 months was 0.09 (95% CI: -0.13, 0.31; p = 0.4167). Figure 1 demonstrates the overlaid distribution of BMI z-score at baseline, 3 months, and 6 months with Kernel smoothed continuous curves. A right shift in the curves signifies an increase in BMI z-score over time, though most drastically seen between baseline and 3-months. The mean difference in pancreatic enzyme dosage between baseline and 3 months was -35.6 units/kg/meal (95% CI: -59.4, -11.8; p = 0.0048), 6 months was -42.16 (95% CI: -107.9, 23.6; p = 0.1944), and 12 months was -132.8 (95% CI: -358.4, 92.9; p = 0.2259). There were no other clinically or statistically significant differences seen with the other growth metric endpoints. The median difference in number of antibiotic courses administered between baseline and the study period was -2.0 (IQR: -3.0-0.0; p = 0.0016). The median difference in the number of hospital admissions between baseline and study period was 0.0 (IQR: -1.0-0.0; p = 0.3750).
Conclusions: This study found that elexacaftor/tezacaftor/ivacaftor therapy benefits CF patients by maintaining their BMI z-score. Pancreatic enzyme dose reduction at 12 months may indicate a clinically significant decrease over time. In addition, a significant difference was found in the number of antibiotic administrations compared to the baseline period. Although our sample size was likely too small to detect a true difference in hospital admissions, a reduction was seen compared to baseline. A larger sample size and longer follow-up period would be helpful to further characterize the extrapulmonary benefits of elexacaftor/tezacaftor/ivacaftor therapy. Based on these results, the team will standardize assessment of growth metrics and enzyme dosage at each visit.
Acknowledgements: The authors received no financial support for the research, authorship, and/or publication of this article.
