Efficacy and safety of the CFTR-modulator lumacaftor/ivacaftor use in patients with cystic fibrosis in different age groups
Authors:   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia, Kondratyeva E.I. , Fatkhullina I.R. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia, Zhekaite E.K. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia, Sherman V.D. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia, Voronkova A.Yu. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russia
Published: October 2024

Russia’s first registered CFTR-modulator lumacaftor/ivacaftor was developed for patients with cystic fibrosis (CF) with the F508del/F508del genotype. The purpose of this research was to study the efficacy and safety of lumacaftor/ivacaftor therapy in different age groups. Materials and methods used: the data of homozygotes for F508del aged 2 to 18 y/o in the Russian CF Patient Registry who had been treated with lumacaftor/ivacaftor were analyzed. The effectiveness of therapy was evaluated in 3 age groups based on examination data, nutritional status, spirometry, sweat test at the start of therapy and after 12 months. In order to assess the safety, examination data, assessment of adverse events (AE), blood biochemical parameters, blood pressure and lens condition were taken into account in 334 pediatric patients in the first month of therapy and in 180 after 12 months. Results: decrease in sweat conductivity was noted in three age groups (p<0.001), only in the 2 to 6 y/o age group were negative values obtained in 6.8%. An increase in BMI was observed in the 6 to 12 y/o and 12 to 18 y/o age groups (р<0.001) whilst an improvement in FVC was observed only in the 12 to 18 y/o age group (p=0.015). Changes in biochemical parameters were statistically significant, both downward and upward, only in the age groups of 6 to 12 y/o and 12 to 18 y/o, changing not significantly. Withdrawal of the drug was required in only a single patient with a persistent increase in transaminase level. Fluctuations in blood pressure occurred within the normal age limits. Frequency of AE was comparable with the results of other studies, it was noted at the start in all groups and after 12 months more often in the age group of 12 to 18 y/o. The best tolerance was noted in the age group of 2 to 6 y/o. Conclusion: for the first time, the efficacy and tolerability of lumacaftor/ivacaftor in patients with CF in Russia was studied against the age aspect according to the 2022-2024 Registry. In the 2 to 6 y/o age group, the achievement of normal sweat test values and the lowest number of adverse reactions were noted, while in the 12 to 18 y/o age group, the positive dynamics were noted for a greater number of indicators, incl. an increase in FVC.