Work

Assessing Safety of Discontinuing Hypertonic Saline in Those with Lower Forced Expiratory Volume in 1 Second after Elexacaftor/Tezacaftor/Ivacaftor

Year: 2023

Type: article

Abstract: Assessing Safety of Discontinuing Hypertonic Saline in Those with Lower Forced Expiratory Volume in 1 Second after Elexacaftor/Tezacaftor/IvacaftorTo the Editor:With the widespread introduction of highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator therapy (HEMT), many people with CF (pwCF) and care providers want to know whether daily therapies can be used less often without sacrificing health improvements that are attributable to HEMT (1).In parallel, randomized controlled trials, the SIMPLIFY study compared the continuation with the discontinuation of daily hypertonic saline (HS) or daily dornase alfa (DA) in pwCF in the United States using elexacaftor/tezacaftor/ivacaftor (ETI) for at least 3 months (2).These trials demonstrated no clinically meaningful differences in percent-predicted forced expiratory volume in 1 second (ppFEV 1 ), lung clearance index, symptom reporting, or acute need for antibiotics between groups that continued or discontinued HS or DA for 6 weeks (3).The tested noninferiority margin for the primary outcome was 23% difference in the 6-week change in ppFEV 1 .The absolute difference measured in these trials was 20.32% with HS discontinuation and 0.35% with DA discontinuation.In this first randomized controlled trial to consider simplifying daily therapies after starting ETI, enrollment was cautiously limited to people with a baseline ppFEV 1 >60%.The observed baseline mean ppFEV 1 was 97% in both trials (3).The difficulty in generalizing these results to those with lower lung function was recognized, and after interim review and approval of safety data, a preplanned, independent substudy within the SIMPLIFY trial randomized pwCF on ETI with a baseline ppFEV 1 of 40-59% to continue or discontinue HS.Analyses included descriptive safety summaries comparing change in ppFEV 1 , collected adverse events, changes in lung function and respiratory symptom scores, and adherence to treatment assignment. Methods

Source: Annals of the American Thoracic Society

DOI: 10.1513/annalsats.202308-735rl