Elexacaftor/Tezacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is the newest cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug approved for the treatment of patients with cystic fibrosis (pwCF) aged ≥6 years with at least one copy of the F508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with ETI. This study determined the effectiveness and safety of ETI in a cohort of severely affected pwCF with an F/F genotype. Methods: Retrospective observational study in F/F pwCF treated for 48 weeks, enrolled in an ETI managed access program available to subjects with advanced lung disease (ppFEV1 < 40). Twenty-six patients from three centres were included. The main outcomes included lung function, sweat chloride concentration (SCC), nutrition, frequency of pulmonary exacerbations (PEx), CFQ-R, and safety. Results: ppFEV1 improved by 12.06 (95%CI 8.54, 15.57) from baseline after 4 weeks of treatment with ETI, 15.32 (11.3, 19.34) after 24 weeks, and 14.48 (10.64, 18.32) after 48 weeks. The increase in FEV1 was accompanied by a decrease in SCC, improvement of BMI, and noticeable reduction in PEx. An overall good safety profile was observed. Conclusions: In F/F pwCF with advanced lung disease with an F/F genotype, ETI was safe and associated with clinical improvement.

Longitudinal Study of Therapeutic Adherence in a Cystic Fibrosis Unit: Identifying Potential Factors Associated with Medication Possession Ratio

“…It is true that with the advent of ETI [ 7 , 8 ], patients’ lives have improved substantially, reducing cough, expectoration, and exacerbations and, improving digestive symptomatology and nutritional status, increasing lung function and quality of life. Thus, the onset of ITD provides an opportunity to consider reductions in the overall treatment burden [ 37 ] and assess whether other chronic medications can be safely discontinued without loss of clinical benefit.…”

“…Until a few years ago, the existing therapies were only aimed at alleviating the symptoms caused by the disease: physical exercise, physiotherapy, bronchodilators, hypertonic or mucolytic substances to improve mucociliary clearance, immunomodulators, and antibiotics to control inflammation and bronchial infection, dietary recommendations, pancreatic enzymes, and vitamin supplements to maintain a good nutritional status [ 3 ]. In recent years, CFTR (transmembrane conductance regulator protein) modulation therapy has been developed, including correctors such as Lumacaftor, Tezacaftor, and Elexacaftor and enhancers such as Ivacaftor, which respectively repair and activate chloride channel function, improving the characteristics of secretions from all organs [ 4 , 5 , 6 , 7 , 8 ]. These treatments are currently indicated in patients heterozygous or homozygous for the F508del mutation and are leading to a major change in the lives of these patients with minimization of most symptoms, which may result in a reduction or abandonment of symptomatic treatment [ 4 , 5 , 6 , 7 , 8 ].…”

“…In recent years, CFTR (transmembrane conductance regulator protein) modulation therapy has been developed, including correctors such as Lumacaftor, Tezacaftor, and Elexacaftor and enhancers such as Ivacaftor, which respectively repair and activate chloride channel function, improving the characteristics of secretions from all organs [ 4 , 5 , 6 , 7 , 8 ]. These treatments are currently indicated in patients heterozygous or homozygous for the F508del mutation and are leading to a major change in the lives of these patients with minimization of most symptoms, which may result in a reduction or abandonment of symptomatic treatment [ 4 , 5 , 6 , 7 , 8 ].…”

Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease

“…Across all three studies, improvement in percentage of predicted FEV 1 (ppFEV 1 ) indicated better lung function, lower sweat chloride concentrations and a higher Cystic Fibrosis Questionnaire-Revised respiratory domain (CFQ-R RD) score indicating less respiratory symptoms and a better overall quality of life ( Zaher et al, 2021 ). Furthermore, an observational study in PwCF homozygous for the F508del mutation ranging from 20.8 to 48.3 years old (median age = 31.1 years) taking TRIKAFTA ® over the course of 48 weeks was done ( Carnovale et al, 2022 ). Although inflammation was not evaluated, an improvement in FEV 1 , body mass index and sweat chloride was observed.…”

“…However, it is important to note that due to COVID-19, CF clinics have seen less bacterial exacerbations since patients were isolating and wearing masks. This is relevant given it is a retrospective study (i.e., without adequate control group comparisons) ( Carnovale et al, 2022 ).…”