Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the newest CFTR modulator approved for patients with cystic fibrosis. In randomized controlled trials, ELX/TEZ/IVA showed benefit at 24 weeks in terms of lung function, respiratory symptoms, pulmonary exacerbations and weight. However, long-term clinical benefit of ELX/TEZ/IVA in real-world settings is still being investigated. Methods This retrospective within-groups study examined cystic fibrosis patients receiving care from a single academic health-system specialty pharmacy. Subjects were included who initiated ELX/TEZ/IVA and continued therapy for greater than one year. Retrospective data from the index year prior to ELX/TEZ/IVA initiation and the year following was collected by medical records review. The primary end point was the difference in number of severe cystic fibrosis exacerbations in index year as compared to the year post ELX/TEZ/IVA initiation. Results A total of 76 patients were included in the final analysis. In the post- ELX/TEZ/IVA year, subjects had a significant mean decrease in severe exacerbations (-0.72; 95% CI -0.43, -1.02; p<0.0001). Decreases in severe exacerbations remained significant in subgroups of patients with prior CFTR exposure (-0.56; 95% CI -0.22, -0.91; p =0.002; n=46) and moderate to severe lung disease (-0.98; 95% CI -0.49, -1.45; p = 0.0002; n=41). After one year of ELX/TEZ/IVA therapy, subjects experienced a significant mean absolute increase in ppFEV1 of 6.07% (between-years difference 4.47%; 95% CI 0.58, 8.37; p=0.025) and increase in BMI of 1.46 (between-years difference 1.29; 95% CI 0.65, 1.95; p=0.0002). Conclusion One year of ELX/TEZ/IVA therapy was associated with sustained improvements in clinical status of cystic fibrosis patients.

Introduction Cystic fibrosis (CF) related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease and can progress to need liver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator which has superior efficacy compared to previously approved modulators. Use of elx/tez/iva, should be approached with caution in individuals with CFLD or following liver transplantation due to possible increases in LFTs and drug-drug interactions with several immunosuppressant medications. Objective The purpose of this case series was to explore if the use of elx/tez/iva is safe and tolerable in patients with CF post-liver transplantation. Methods A retrospective case series including patients prescribed elx/tez/iva following liver transplantation and an immunosuppressive regimen consisting of drug therapy metabolized by P-glycoprotein was completed. Results Ten patients at six CF centers with a median age of 22.1 years (range 14-43.4 years) and median time from transplant of 6.9 years (range 0.6-22 years) were included. Most patients (8, 80%) received a reduced or full dose of elx/tez/iva for a mean duration of 10.4 months (range 7-12 months). Fluctuations in LFTs occurred in all patients (10, 100%) and led to therapy discontinuation in two patients (20%). Elx/tez/iva initiation resulted in elevations in tacrolimus trough concentration in 7 patients (70%). Most patients who tolerated elx/tez/iva had symptomatic and quality of life improvement, increased body-mass-index, and maintained or improved lung function. Conclusion Initiation of elx/tez/iva in patients with CF who received a liver transplantation may be safe with clinical benefits.