Features of the appointment of enzyme replacement therapy in children with Cystic Fibrosis in the Russian Federation. Cross-sectional study

Abstract

Relevance: Controversial issues of enzyme replacement therapy for cystic fibrosis continue to be studied, without losing relevance against the background of taking targeted drugs. Studies show that there is a large scale in the dosage of pancreatin that goes beyond the recommended values and there is no unified approach to prescribing the drug related to national and individual characteristics. Currently, there is insufficient data to substantiate consensus recommendations on enzyme therapy from the standpoint of evidence-based medicine. There is a need for scientific substantiation of the accepted therapeutic algorithm, search for optimal doses, calculation methods, correction, development of an individual approach to the appointment of pancreatin in cystic fibrosis. Objective: to study the features of pancreatin dosing in children with pancreatic insufficiency of cystic fibrosis in the Russian Federation Material and methods. 140 children (boys - 73, girls - 67) with CF aged from 1 year to 18 years (average age 8,9±5,8 years) were examined in the Department of cystic Fibrosis Scientific and Clinical Institute of Childhood of the Ministry of Health of the City of Mytishchi (clinical base of the scientific and clinical Department of cystic fibrosis). The study was conducted in 2018. The nutritional status (anthropometric indicators) of the pancreatin dose per day and for each meal was assessed using 2 calculation methods: units/kg of body weight and units/g of fat in food. Separately, these indicators were analyzed in a group of patients homozygous for the genetic variant F508del of the CFTR gene Design: cross-sectional study Results. The study showed that 67% of patients in the general group and 68% in the subgroup of patients homozygous for the genetic variant F508del of the CFTR gene received doses of pancreatin in reference values (up to 10,000 EU/kg of body weight per day). When calculating the pancreatin dose by the method per gram of fat in food, most of the patients (59%) in the general group and 47% of patients in the F508del homozygous subgroup received pancreatin doses of less than 2000 EU/g of fat, which is less than the reference values (2000-4000 EU/g). The results are consistent with the data of recent studies indicating an acceptable dosage range of pancreatin 1000-4000 EU/g of fat in food. The median daily dose of pancreatin of the subgroup with the genetic variant F508del of the CFTR gene was 1700 EU/g of fat in food, and in the general group 1500 EU/g of fat (p≥0.05), which can be attributed to the peculiarities of dosing and the need for pancreatin in the Russian pediatric population of patients with cystic fibrosis. The BMI percentile did not differ in subgroups with different doses of pancreatin when calculated by two calculation methods. The median daily dose of pancreatin in patients homozygous for the genetic variant F508del of the CFTR gene and the general group did not differ statistically. Conclusion. Most of the children in the general group and in the subgroup of homozygous F508del genetic variant received pancreatin in the range of 6000-10000 EU/kg of body weight. Most patients in the general group received less than 2000 EU/g of fat, unlike the subgroup with the F508del/F508del mutation - 2000-4000 EU/g of fat (p≥0.05). The median pancreatin of the subgroup with the F508del/F508del mutation was 1700 EU/g of fat in food, in the total group 1500 EU/g of fat (p≥0.05). High doses of pancreatin are not associated with nutritional status (BMI percentile).