Effectiveness of lumacaftor/ivacaftor in 1-year therapy of cystic fibrosis in adult patients

Abstract

Introduction. Cystic fibrosis is a severe systemic multiorgan exocrinopathy, the severity of the condition in 95% cases is caused by the depth of respiratory organ damage. Symptom management drugs that were developed over more than 50 years allowed to improve survival, but average life expectancy in cystic fibrosis (CF) remains well below the general population average. Targeted therapy is the most promising treatment, which restores the chloride channel function. Lumacaftor/ivacaftor is the first targeted therapy drug authorized in Russia.Aim. To evaluate the effect of lumacaftor/ivacaftor therapy on the respiratory function, microbiological profile, nutritional and oxygen status, as well as the rescue antibiotic therapy coverage in adult patients with CF.Materials and methods. 39 adult patients with CF received lumacaftor/ivacaftor for one year. The therapy effectiveness endpoints included the changes in indices of the pulmonary function tests: FEV1, FVC, FEV1/FVC, sweat test results, nutritional and oxygen status, antibiotic therapy coverage. The tolerability of the drug was assessed. The median age of patients was 28.9 (11.3) years. 6 patients (15.4%) discontinued therapy due to different adverse reactions.Results. The median increase in FVC was 2.9 (4.1)%, in FEV1 – 3.1 (4.1)%, sweat chloride decreased by 21 (27) mmol/l during 1–1.5-month lumacaftor/ivacaftor therapy. After 12-month therapy, the median increase in FVC was 2.3 (3.6)%, in FEV1 – 2.4 (3.8)%, BMI increased by 0.6 (0.6) kg/m2 and the frequency of rescue antibiotic therapy decreased by half. The patients showed a significant increase in FVC and FEV1 indices and a decrease in sweat chloride after 1-month therapy and an increase in FEV1 indices, BMI vales as well as a reduced need for rescue antibiotic therapy after 12-month therapy.Conclusion. The first experience with a long-term pathogenetic therapy with lumacaftor/ivacaftor in adult patients with CF in Russia demonstrated the expected positive effect on the respiratory function and changes in nutritional status, a reduced need for rescue antibiotic therapy, and low rates of adverse reactions.