Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis

Author:

Pingree Graham1ORCID,Bentan Mihai2,Fitzpatrick Thomas2,Schuman Theodore2ORCID

Affiliation:

1. Department of Otolaryngology Virginia Commonwealth University School of Medicine Richmond Virginia USA

2. Department of Otolaryngology–Head and Neck Surgery Virginia Commonwealth University Virginia Commonwealth University School of Medicine Richmond Virginia USA

Abstract

AbstractBackgroundElexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear.MethodsThe TriNetX Analytics Research Network, consisting of 120 million global de‐identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA‐approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF‐related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS.ResultsETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5–2.75; p‐value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54–5.85; p‐value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non‐CFTR modulator groups, except for reduced CF‐related pulmonary exacerbations from 0 to 6 months post‐FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators.ConclusionsIn a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.

Publisher

Wiley

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