Real -world impact of previous exposure to CFTR modulators on clinical parameters and chronic sinus disease in people with cystic fibrosis on elexacaftor-tezacaftor-ivacaftor

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BACKGROUND: The impact of previous exposure to CFTR therapies on efficacy of Elexacaftor-tezacaftor-ivacaftor (ETI) therapy is unclear. OBJECTIVE: Objective of this study was to quantify differences in clinical parameters and chronic sinus disease with ETI therapy among those naive and previously exposed to CFTR modulator therapies. METHODS: Our cohort included 115 pwCF, median (IQR) age of 23 (17, 32) years. Clinical data was collected at initiation of ETI therapy and at three-month intervals for one year. Twenty-one pwCF with sinus CT scan performed within three-months of initiation of ETI therapy (baseline) and after one-year on ETI therapy were included in this study, and changes were compared using both Lund-Mackay (LM) and Sheikh-Lind (SL) sinus CT scoring systems. RESULTS: and BMI were observed (p < 0.001), and change was independent of previous CFTR modulator exposure (p = 0.5 and 0.4 respectively). Similarly, significant reduction in median sinus CT scores were noted, median total score of LM sinus CT scoring system decreased from 5.5 to 2.8 (p < 0.001) and SL score decreased from 3.8 to 2.2 (p < 0.001) and changes were independent of previous CFTR exposure. CONCLUSION: ETI therapy was associated with improved clinical outcomes and improvement in sinus CT scans in pwCF and changes were independent of previous CFTR modulator therapies.

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