Real-World Impact of Elexacaftor/Tezacaftor/Ivacaftor in Israeli Children Aged 2-6 With Cystic Fibrosis.

BACKGROUND

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators revolutionized the care of people with Cystic fibrosis (pwCF) by addressing the underlying genetic defect rather than merely managing symptoms. Elexacaftor/Tezacaftor/Ivacaftor (ETI) has shown significant clinical benefits in pwCF carrying specific CFTR mutations; however, data on its safety and efficacy in young children with CF (ycwCF), aged 2-6 years, remain sparse.

METHODS

We conducted a real-world, retrospective study that included all Israeli ycwCF who were genetically eligible for and treated with ETI. Body mass index (BMI) z-score, forced expiratory volume in one second (FEV1) percent predicted, rate of pulmonary exacerbations (PEx), sweat conductivity levels, bacterial sputum isolates, clinic visits frequency, and sputum samples collected before and after ETI initiation were evaluated. Additionally, adverse effects were assessed.

RESULTS

Sixteen ycwCF, aged 2-6 years, received ETI therapy for a mean duration of 13 months (range 4-25 months), including three pancreatic-sufficient patients. Following ETI initiation, significant improvements were observed. BMI z-scores increased from -0.37 ± 1.32 to -0.01 ± 1.14 (p = 0.005), and in the subset of patients tested (7/16), FEV1 improved from 91 ± 12 to 113 ± 18 percent predicted (p = 0.018). The rate of PEx decreased from 0.7  ±  1.1 to 0.2  ±  0.4 (p = 0.058) and sweat conductivity levels dropped significantly from 112  ±  38 to 48  ±  30 mmol/L (p = 0.002). There was a marked reduction in bacterial colonization in sputum: Pseudomonas aeruginosa declined from 9/16 to 2/14 (p = 0.04), and Staphylococcus aureus from 12/16 to 2/14 (p = 0.01). Notably, the total number of sputum cultures sent also decreased by 35%, from 116 before ETI to 75 after treatment initiation. This reduction paralleled decreased CF clinic visits, from 7.3  ±  3 per year to 4.7  ±  3 (p = 0.001). Reported adverse effects were minimal, and no treatment discontinuations were required.

CONCLUSIONS

These real-world findings support the safety and effectiveness of ETI in ycwCF. Robust, long-term studies involving larger populations are essential to confirm these results.