FIRST RESULTS OF TREATMENT WITH TWO CFTR-MODULATORS FOR CYSTIC FIBROSIS IN CHILDHOOD
Authors:   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russia, Kondratyeva E.I. ,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Odinaeva N.D. ,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Sherman V.D. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russia,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Voronkova A.Yu. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russia,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Zhekaite E.K. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russia,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Pasnova E.V. ,   Research Clinical Institute of Childhood of the Moscow Oblast Regional Ministry of Healthcare, Moscow, Russia, Kutsev S.I. ,   Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russia
Published: May 2022

In the treatment of cystic fibrosis (CF), new methods of precision medicine have emerged. This is due to the discovery of pathogenetic modulator drugs that eliminate the main defects in pathogenic variants of the CFTR gene. Objective of the study: to analyze the efficacy and safety of two CFTR modulators in children with CF. Materials and methods of research: a single-center, experimental, open, controlled, non-randomized study was conducted from November 2021 to March 2022, 2 groups were studied: 1st group [23 patients (7 M/16 F), homozygous for F508del with confirmed homozygosity and exclusion of the F508Del; L467F complex Allela] received ivacaftor/lumacaftor; 2nd group [20 patients (6 M/14 F), compound heterozygous for F508del or other pathogenic variants of the CFTR gene] received an elexacaftor/tezacaftor/ivacaftor. We studied the dynamics of indicators at the start and after 3 months: sweat test, body mass index (BMI), external respiration (ER), levels of ALT, AST, total bilirubin, blood pressure (Bp). Results: when using ivacaftor/lumacaphore in 23 patients, the median age ME (Q1–Q3) 14.8 (11.3–16.2) years, a statistically significant increase in body weight: from 38.8 (28.6–48,4) kg up to 44.8 (29.4–52.1) kg after 3 months (p=0.007), decrease in sweat conductivity (mmol/l) Me (Q1–Q3) 113.0 (100–120) at the start, 89.0 (76–92.5) after 3 months (p=0.012) was noted. Unwanted side effects (USEs) are registered in 47.8% of cases. When evaluating the effectiveness of the elekfator/thezacaftor/ivakaftor drug in 20 patients (6 M/14 F), the median age ME (Q1–Q3) 15.5 (13.6; 16.8) of the year revealed a statistically significant increase in body weight from 44,4 (39.6–52.1) kg at the start of up to 50.0 (43.1–54.1) kg after 3 months (p=0.003), BMI from 17.3 (16.5–19.7) percentil at the start of up to 19.0 (17.7–19.9) percentil after 3 months (p=0.002), forced vital capacity (FVC) (%due) from 73.0 (59.6–84.8) at the start of up to 86.0 (74.5–97.0) after 3 months (p=0.002), forced expiratory volume in the 1st second (FEV1) (%due) from 75.5 (51.1–78.8) at the start of up to 85.0 (68.5–106.0) after 3 months (p=0.002), reduction of sweat conductivity from 104.0 (95–123.5) mmol/l at the start of up to 64.0 (53–78) after 3 months (р=0.008) was noted. USEs were noted in 30%. Cancellation of the drug was not required. Conclusion: assessment of the results of therapy with targeted drugs demonstrated better tolerance and effectiveness of therapy with an elexacaftor/tezacaftor/ivacaftor compared to ivacaftor/lumacaftor, which indicates the advantage of this CFTR modulator.