The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis post-liver transplant: a case series

Abstract

Introduction Cystic fibrosis (CF) related liver disease (CFLD) manifests\nas a wide spectrum of hepatobiliary disease and can progress to need\nliver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is\na cystic fibrosis transmembrane conductance regulator (CFTR) modulator\nwhich has superior efficacy compared to previously approved modulators.\nUse of elx/tez/iva, should be approached with caution in individuals\nwith CFLD or following liver transplantation due to possible increases\nin LFTs and drug-drug interactions with several immunosuppressant\nmedications. Objective The purpose of this case series was to explore if\nthe use of elx/tez/iva is safe and tolerable in patients with CF\npost-liver transplantation. Methods A retrospective case series\nincluding patients prescribed elx/tez/iva following liver\ntransplantation and an immunosuppressive regimen consisting of drug\ntherapy metabolized by P-glycoprotein was completed. Results Ten\npatients at six CF centers with a median age of 22.1 years (range\n14-43.4 years) and median time from transplant of 6.9 years (range\n0.6-22 years) were included. Most patients (8, 80%) received a reduced\nor full dose of elx/tez/iva for a mean duration of 10.4 months (range\n7-12 months). Fluctuations in LFTs occurred in all patients (10, 100%)\nand led to therapy discontinuation in two patients (20%). Elx/tez/iva\ninitiation resulted in elevations in tacrolimus trough concentration in\n7 patients (70%). Most patients who tolerated elx/tez/iva had\nsymptomatic and quality of life improvement, increased body-mass-index,\nand maintained or improved lung function. Conclusion Initiation of\nelx/tez/iva in patients with CF who received a liver transplantation may\nbe safe with clinical benefits.