Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease with the Phe508del/minimal function genotype

Background: Elexacaftor/tezacaftor/ivacaftor (E/T/I) is a cystic fibrosis transmembrane conductance regulator (CFTR) triple combination therapy used for the treatment of cystic fibrosis (CF) in patients aged ≥12 years who have at least one copy of the Phe508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with E/T/I. This study determined the effectiveness and safety of E/T/I treatment in a cohort of CF patients. Methods: This retrospective cohort study collected data from the first 6 months of treatment of patients with CF, compound heterozygotes for the F and a minimal function (MF) mutations, enrolled in an E/T/I compassionate use program only available to patients having ppFEV1<40 or who are considered for lung transplantation. Forty-seven patients were included. Follow-up was performed after 1, 3, and 6 months from the beginning of therapy, assessing lung function, body mass index (BMI), sweat chloride concentration (SCC), quality of life (QoL), and safety. Results: After 6 months of treatment, the mean (standard deviation (SD)) SCC decreased from 91.1 (19.3) mmol/L to 46.2 (24.2) mmol/L. The decrease of SCC was accompanied by improvement of lung function (mean (95% Confidence Interval (CI) absolute increase in ppFEV1 was 10.69 (8.05,13.33) after 1 month and 14.16 (11.43, 16.89) after 6 months of treatment), nutrition (mean (SD) BMI increased from 20.7 (3.0) kg/m2 at baseline to 22.6 (3.1) after 6 months), and QoL. No safety concerns were observed. Conclusions: E/T/I was clinically effective and safe in patients with advanced CF lung disease with an F/MF genotype.