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.

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

Among the total cohort of 115 pwCF, 49 (42.6 %) were naive to CFTR modulators and the remaining 66 (57.4 %) were previously exposed to CFTR modulators before switching to ETI. With one-year of ETI therapy, significant increases in ppFEV1 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.