Extrapulmonary benefits and pharmacogenomics in lung transplant recipients with Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy.

Abstract

Elexacaftor/Tezacaftor/Ivacaftor (ETI) and other highly effective modulator therapies have transformed outcomes for people with cystic fibrosis (pwCF), yielding significant pulmonary and extrapulmonary benefits. Although lung transplant (LTx) rates have declined dramatically in the post ETI era, a substantial number of transplant recipients with CF remain who may benefit from the extrapulmonary effects of these therapies. Unfortunately, available post market data regarding ETI safety, efficacy, and tolerability following LTx are limited and conflicting, raising concerns for Drug-Drug Interactions (DDI) and long-term graft function. In this single center retrospective cohort analysis, we report sustained improvements in sinonasal disease and weight maintenance with preserved spirometric values over a mean follow up of 35.1 months on ETI compared to those not on therapy. We additionally present pharmacogenomic testing in a subset of our cohort as proof-of-concept for predicting DDIs at time of initiation of ETI.