In the Russian Federation, patients with cystic fibrosis (CF) under 19 years of age receive targeted therapy with two drugs: lumacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor. Currently, a large volume of information has accumulated regarding possible adverse drug reactions (ADRs) during long-term targeted therapy in children with CF.   The aim of the study was to investigate the ADR profile associated with long-term use of CFTR modulators in children with CF.   Methods. Data on the targeted therapy were taken from the Russian registry of CF patients (2021 – 2024). The data of 392 patients at the start of therapy with lumacaftor/ivacaftor, 196 patients after 1 year, and 36 patients after 2 years were analyzed. The data of 220 patients at the start of therapy with elexacaftor/tezacaftor/ivacaftor, 214 patients after 1 year, and 43 patients after 2 years were analyzed. Early adverse reactions were assessed within 30 days from the start of therapy. Change in the adverse reaction profile was assessed after 360 and 720 days.   Results. The number of adverse reactions in patients receiving lumacaftor/ivacaftor was 51.27 % for 1 month. It decreased more than 2-fold (20.4 %) by the end of the 1st year (p1–2 < 0.001) due to a decrease in the number of patients with cough, shortness of breath, elevated alanine aminotransferase (ALT) / aspartate aminotransferase (AST) levels, and diarrhea. After 2 years, the incidence of adverse reactions was 55.5 % (p2–3 < 0.001), the number of patients with subfebrile body temperature/fever increased (p2–3 < 0.001; p1–3 < 0.001), the rate of fatigue increased to 11.1 % (p2–3 = 0.029), and the rate of sleep disturbance increased (from 0.25% at the start to 11.1 % after 2 years of therapy; p1–3 < 0.001; p2–3 < 0.001). The average incidence of adverse reactions per patient was 2.27 ± 0.45 for lumacaftor/ivacaftor. The total incidence of ADRs with elexacaftor/tezacaftor/ivacaftor combination therapy was 48.2 % at the start, 19.6 % after 1 year (p1–2 < 0.001), and increased to 41.9 % after 2 years (p2–3 < 0.001) due to subfebrile body temperature/fever – from 1.9 to 6.9 % (p1–3 = 0.032), headache – from 2.3 to 11.6 % (p1–3 = 0.003), and fatigue – up to 13.9 % (p1–3 < 0.001; p2–3 = 0.002). The average incidence of ADRs per patient was 2.56 ± 0.71 with elexacaftor/tezacaftor/ivacaftor combination therapy. More ADRs were observed at the start of therapy with lumacaftor/ivacaftor compared to elexacaftor/tezacaftor/ivacaftor (p = 0.019). The frequency of elevated ALT/AST levels at the start of therapy with lumacaftor/ivacaftor was higher than for elexacaftor/tezacaftor/ivacaftor (p = 0.02). Rash was observed more often at the start of therapy with elexacaftor/tezacaftor/ivacaftor (p < 0.001), fatigue – at the start of lumacaftor/ivacaftor (p = 0.011). No difference in the ADR profile was found after 2 years of therapy.   Conclusion. A higher number of ADRs was associated with lumacaftor/ivacaftor compared to elexacaftor/tezacaftor/ivacaftor. Over time, the main adverse drug reactions associated with respiratory and gastrointestinal symptoms resolve, but the number of patients complaining of fatigue, sleep disturbances, headaches, subfebrile temperature and fever increases, requiring active follow-up and adjustment of the therapy if necessary.

The aim of the program was to study the tolerability of Tigerase® in patients with cystic fibrosis (CF) of all ages in rutine clinical practice. Study design: retrospective open uncontrolled comparative multicenter solid. Materials and methods of research: retrospective data of clinical observations were collected from medical records of patients with CF on the use of Tigerase®. Results: therapy with Tigerase® was well tolerated by 668 (93,4%) of 715 patients included in the study. In 47 (6,6%) patients, 127 adverse reactions (ADRs) associated with the use of Tigerase® were recorded. ADRs from the respiratory system were the most common. Of these, 24 (3,4%) were coughing and 10 (1,4%) had increased viscosity of bronchial secretion. Among all patients included in the study, the proportion of patients in whom ADRs were registered based on clinical manifestations (3,9%) did not differ statistically significantly from the proportion of patients in whom ADRs were recorded based on complaints only (2,8%) (p=0,30). The distribution of ADRs by the source of registration and place of residence of patients did not depend on their gender and age. Registration of ADRs in different regions of the country differed statistically significantly both in frequency and in the source of detection (p<0,001). ADRs were not recorded in several regions, and the largest number of ADRs were registered in patients living in Moscow, and most of them were based only on patient complaints. 22 patients (47% of the number of patients with ADR) had medical commissions for ADR, and only in 8 (17% of the number of patients with ADR) of them had expertise of specialists with experience in the treatment of patients with CF. In 29 patients (62% of the number of patients with ADR), the development of ADR did not require cessation of the Tigerase® therapy. Conclusion: in the majority of CF patients (93,4%) tolerated the Tigerase® therapy well.

Cystic fibrosis (CF) is a severe hereditary disease that leads to decreased lung function. Objective. To assess the dynamics of lung function changes in CF patients living in the Volga Federal District (VFD) regions based on data from the 2017 and 2023 registries. Material and methods. Spirometry data from 375 patients from the 2017 CF patient registry and 451 patients from the 2023 registry were analyzed. Results. The median FEV1 data in VFD patients was 76.8% of the predicted value in 2017 and significantly increased to 95.3% of the predicted value in 2018. in 2023 (p<0.001). In 2017, FEV1 values in patients with CF in the Volga Federal District were not significantly different from those in the Russian Federation (75.5% of the predicted value), while in 2023, they were significantly higher than in patients in other regions of Russia (81.1% of the predicted value), p<0.001. FEV1 values increased significantly in patients from the Nizhny Novgorod Region, Orenburg Region, Perm Krai, the Republic of Tatarstan, and the Chuvash Republic. The median FVC in patients with CF from the Volga Federal District in 2017 was 85.1% of the predicted value and significantly increased to 94.0% of the predicted value in 2023 (p<0.01). In 2017, the FVC indicators in patients with CF in the Volga Federal District did not differ significantly from those in patients in the Russian Federation (86.0% of the predicted value), and in 2023 they were significantly higher than in patients in other regions of Russia (91.0% of the predicted value), p=0.037. The FVC indicators in 2023, compared with 2017, significantly increased in patients in the Nizhny Novgorod Region (p<0.001), Orenburg Region (p<0.001), Perm Krai (p=0.021), the Republic of Tatarstan (p=0.043), and the Chuvash Republic (p=0.003). In patients in the Samara Region, the indicators remained stable (p=0.331). Conclusions. FEV1 and FVC values in CF patients in both the Volga Federal District and the Russian Federation increased significantly in 2023 compared to 2017. Patient data from Volga Federal District regions where specialized CF centers were established were more informative, and patients had higher lung function values.

Objectives: The establishment of cystic fibrosis (CF) databases allows caregivers to compare different approaches and improve CF care. The longitudinal data allows the understanding of trends in CF clinical course. We present the 9 years data of the Israeli CF Patient Registry. Methods: Epidemiological, genetic and clinical data from all CF patients were entered into database registry during the years 2005-13. Results: 529 patients were followed in 2013, 58% of them adults (>18 yrs), compared to 498 in 2005, 47% adults (p = 0.048). Median FEV 1 improved from 79% predicted in 2008 to 82.5% predicted in 2013 (p = 0.015). Despite the improved outcome the prevalence of CF decreased from 1:14,000 in 2005 to 1:15,370 in 2013 (p = 0.004), probably due to less CF births. The median age at diagnosis was 0.7 y (0-65 y), meconium ileus was the presenting symptom in 14%. W1282X and delF508 were the most common CFTR mutations (23% each). Chronic growth of P. aeruginosa in sputum was observed in 40% of patients compared to 32% in 2005 (p = 0.043). Staphylococcal colonization increased from 14% to 34% in these years (p < 0.05). Median BMI-SDS in CF children was-0.1. CF adults had median BMI of 22.5 (females 20.8, males 22.9) compared to 21.2 in 2007 (p < 0.05). CF related diabetes was reported in 11% in 2005 and 19% in 2013 (p = 0.001). Conclusions: CF patients in 2013 are older and having better lung function and nutritional status, possibly due to improved care but with higher prevalence of bacterial colonization.