P049 Effects of elexacaftor/tezacaftor/ivacaftor after 6 months in Dutch people with cystic fibrosis with at least 1 F508del mutation

Objectives: To evaluate the effect of elexacaftor/tezacaftor/ivacaftor in The Netherlands for people with CF (pwCF) of 12 years and older with at least 1 F508del mutation after 6 months of use. Methods: Our study is a prospective observational cohort study in which we report real life data on the use of elexacaftor/tezacaftor/ivacaftor. Our primary endpoint is the change in percent predicted FEV1 (ppFEV1) and secondary endpoint change in SCC and the correlation between change in ppFEV1 and change in SCC. Results: We enrolled 185,169 (82.8%) F508del homozygous patients and 35 (17.2%) heterozygous patients with 1 F508del mutation. The baseline mean ppFEV1 was 72% and the mean SCC was 84.4 mmol/L. After 6 months of elexacaftor/tezacaftor/ivacaftor there was a significant increase in ppFEV1 of 13.8% and a significant decrease in SCC of 50.1 mmol/L. There was no significant correlation between change in ppFEV1 and change in SCC. In the subanalysis, female patients had a higher increase in ppFEV1 of 4.7% compared to men. PwCF who did not use another CFTR modulator before, showed a ppFEV1 increase which was 5.5% higher compared to those that were on CFTR modulators before. In addition, the increase in ppFEV1 was higher in patients with an FEV1>90% compared to FEV1<90%, and the increase was higher in heterozygous patients compared to homozygous patients (non-significant), probably due to the fact that these patients already used another CFTR modulator. The analysis of the change in SCC was only significantly different between female and male patients. In the female pwCF the SCC decreased 11.8% more compared to the group of male pwCF. Conclusion: In conclusion, our real life data on the use of elexacaftor/tezacaftor/ivacaftor show a substantial increase in lung function and decrease in SCC in our cohort of Dutch people with CF older than 12 years of age with at least 1 F508del mutation. In addition, we need more biomarkers to monitor the effect of CFTR modulators.