Evaluating the effect of СFTR modulators on lung function in children with cystic fibrosis with F508del/F508del genotype

Background. The therapy of CFTR modulators for cystic fibrosis (CF) patients is a priority task. Since November 2021, children and adolescents with CF in Russia have been provided with the lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor + ivacaftor treatment, funded by the «Krug Dobra» (Circle of Goodness) Foundation. The impact of therapy on lung function in CF is of great interest and is crucial for evaluating its effectiveness.

Objective: to evaluate the impact of CFTR modulators — lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor + ivacaftor — on lung function in CF patients with the F508del/F508del genotype.

Materials and methods. A retrospective, observational, longterm study of respiratory function data was conducted in children and adolescents with the F508del/F508del genotype receiving therapy with lumacaftor/ivacaftor (n = 96) and elexacaftor/ tezacaftor/ivacaftor + ivacaftor (n = 14) using data from national CF patient registries in 2019 and 2022.

Results. In the general group of patients receiving CFTR modulators, respiratory function indicators did not change statistically significantly. However, they tended to decrease: mediana (Me) FEV1 in 2019 was 85.0% compared to 83.5% in 2022; a decrease in Me FEV1 by 1.5 p.p. Me FVC in 2019 was 89.0% compared to 88.1% in 2022. The decrease in Me FVC was 0.9 p.p. During therapy with lumacaftor/ivacaftor or elexacaftor/tezacaftor/ ivacaftor + ivacaftor, the FEV1 parameters showed no statistically significant changes. In patients receiving therapy with lumacaftor/ivacaftor, Me FEV1 decreased from 85.0% to 81.4%, Me FVC — from 89.0% to 88.1%. Me FEV1 decreased by 3.6 p.p, and Me FVC decreased by 0.9 p.p. In patients receiving therapy with elexafactor/tezacaftor/ivacaftor + ivacaftor, FEV1 parameters tended to increase: Me FEV1 increased from 81.2% to 82.0%, and Me FVC — from 81.4% to 87.0%. Me FEV1 increased by 0.8 p.p, and Me FVC increased by 5.6 p.p.

Conclusions. The conducted assessment of the impact of CFTR modulators on lung function in children revealed that in patients with the F508del/F508 genotype, both FEV1 and FVC values did not decrease statistically significantly in 2022 compared to 2019. This can be considered a positive factor in terms of the impact of therapy on the course of CF. However, under lumacaftor/ivacaftor therapy, FVC values tended to decrease. For comparison, the elexacaftor/tezacaftor/ivacaftor + ivacaftor combination, despite lower baseline FVC values, led to an increase in these indicators.

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