Efficacy and safety of triple therapy (elexacaftor/tezacaftor/ ivacaftor) in children with cystic fibrosis: 12-month follow-up

The most effective drug for targeted therapy of cystic fibrosis (CF) today is the CFTR modulator elexacaftor/tezacaftor/ivacaftor. It is a combination of two CFTR correctors and a CFTR potentiator that correct the main genetic defect in patients with CF who carry at least one genetic variant specified in the instructions for use of the drug. In the Russian Federation, children with CF at the age of 6 years and older are provided with a targeted drug at the expense of the Circle of Kindness Charitable Foundation.

The aim of the study was to investigate the efficacy and safety of therapy with the CFTR modulator elexacaftor/thezacaftor/ivacaftor in children with cystic fibrosis during 12 months of follow-up.

Methods. The data of 48 patients aged 6 to 18 years who received targeted therapy with elexacaftor/tezacaftor/ivacaftor in 2021 and were included in the “Targeted therapy” section of the Register of Patients with Cystic Fibrosis in the Russian Federation, were analyzed. To study the effectiveness and safety of the therapy, the patients’ nutritional status, sweat test, respiratory function, blood chemistry, blood pressure, and lens condition were monitored during the therapy.

Results. During therapy, an increase in body weight was noted from 44.1 (± 8.8) to 50.1 (± 7.8) kg (M ± SD) (p < 0.001); height, from 158.2 (± 9.1) to 161.9 (± 8.7) cm (p < 0.001); and BMI, from 17.5 (± 2.3) to 19 (± 1.9) kg / m2 (p < 0.001). The conductivity of sweat decreased from 114.8 (± 17.4) at the start of triple therapy to 73.9 (± 20.6) mmol/l NaCl (p < 0.001) after 12 months of treatment. In 28.5%, the sweat test results returned to normal (the sweat conductivity was equivalent to < 50 mmol / l NaCl). Statistically significant changes in the indices of respiratory function were obtained: the forced vital capacity increased from 72.8%pred. (± 21.7) to 86.6%pred. (± 24.4) (p < 0.001), FEV1 – from 67.2%pred. (± 21.7) to 84.9%pred. (± 28.9) (p < 0.001).

Conclusion. Analysis of the tolerability showed a consistent safety profile of the triple therapy.

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