Efficacy and safety of elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis after 36 months of therapy

Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene. CFTR modulators are a complex of CFTR protein potenti­ator and correctors that improve chloride channel function. Currently, the most effective targeted therapy drug is the combination of elexacaftor/ tezacaftor/ivacaftor (ETI). However, data on the long-term efficacy and safety of triple combination therapy in real-world clinical practice in the Russian Federation are limited.

The aim is to analyze the efficacy and safety of therapy with the three-component elexacaftor/tezacaftor/ivacaftor based on data from the registry of patients with cystic fibrosis of the Russian Federation for 36 months.

Methods. A retrospective study was conduct­ed using data from the Russian Federation Cystic Fibrosis Patient Registry in the Targeted Therapy section for 2021 - 2024. The study included 900 patients over 6 years old with cystic fibrosis receiving triple targeted therapy with ETI. The following criteria were assessed for the effectiveness of therapy: sweat test, anthropometric data (weight, height, BMI), lung function parameters (FVC and FEV₁ in absolute (L) and relative (% predict­ed) values), at the start of therapy and over 3 years. The following safety criteria were assessed in pairwise comparisons: ALT (U/L), AST (U/L), total bilirubin (^mol/L), systolic and diastolic blood pressure during 3 years of therapy.

Results. Comparison of the sweat test results, FEV1 and FVC, BMI at the start of therapy, after one year, 2 years and 3 years showed a significant decrease in sweat test results, an improvement in anthropometric data (BMI), an increase in absolute and relative indicators of respiratory function (FVC, FEV₁) during the first year of therapy, and stabilization of indicators on during the second and third years of therapy. The safety profile of ETI was characterized by stable median values of ALT, AST, and total bilirubin within the reference values at three-year follow-up. Adverse reactions were reported in 9.4% of cases at the start of therapy. After three years of therapy, the adverse reactions were rare and more related to the mental sphere.

Conclusion. Patients with cystic fibrosis who received three-component ETI therapy showed significant improvement of basic health indicators compared to the initial ones they had while receiving only basic therapy. The long-term efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination has been demonstrated for three years.

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