Medication Utilization and Lung Function Changes

Nine people with cystic fibrosis (pwCF) were found to have isolated elevations in serum total bilirubin after starting elexacaftor/tezacaftor/ivacaftor (ETI) that were associated with Gilbert’s Syndrome. In longitudinal examination, total bilirubin levels increased substantially after initiation of ETI without elevations in liver transaminases in those with this syndrome. Because elevated bilirubin levels in Gilbert’s Syndrome are benign, ETI was able to be continued in these individuals. Genetic testing for this relatively common syndrome should be strongly considered for pwCF experiencing isolated hyperbilirubinemia after starting ETI, since appropriate diagnosis may help pwCF avoid unnecessary interruption in this therapy with significant health benefits in CF.

ETI treatment reduces inflammatory markers and positive bacterial cultures on BAL in PwCF. These findings suggest that ETI has a greater impact on chronic infection and inflammation than ivacaftor alone. However, airway inflammation persists in a fraction of treated individuals, indicating an ongoing need to optimize other treatments in a subset of patients.