The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study

Scott H Donaldson; Timothy E Corcoran; Joseph M Pilewski; Beth L Laube; Peter Mogayzel; Agathe Ceppe; Jihong Wu; Kirby Zeman; Steven M Rowe; David P Nichols; Alex H Gifford; William D Bennett; Nicole Mayer-Hamblett; SIMPLIFY MCC Study teams

doi:10.1016/j.jcf.2024.02.003

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study

J Cyst Fibros. 2024 Feb 13:S1569-1993(24)00018-3. doi: 10.1016/j.jcf.2024.02.003. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine and the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: Scott_Donaldson@med.unc.edu.
² Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
³ Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
⁴ Department of Medicine and the Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Medicine and the Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Seattle Children's Research Institute, Department of Pediatrics, University of Washington, Seattle, WA, USA.
⁷ University Hospitals Cleveland Medical Center and University Hospitals Rainbow Babies and Children's Hospital, Cleveland, OH, USA.

PMID: 38355350
DOI: 10.1016/j.jcf.2024.02.003

Abstract

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Keywords: Clinical trial; Cystic fibrosis; Dornase alfa; Hypertonic saline; Mucociliary clearance; Withdrawal.