Longitudinal follow up of people with cystic fibrosis who discontinued mucoactive therapy during CFTR modulator treatment

<bold>Backgroud:</bold> Kaftrio (elexacaftor, tezacaftor and ivacaftor, ETI) is a highly effective therapy for people with CF(PwCF). Because of clinical improvements observed in PwCF during treatment with ETI the additional benefit of other maintenance therapies is questioned. <bold>Aim:</bold> to evaluate long term treatment response to ETI in PwCF, and compare outcomes in PwCF discontinuing inhaled mucoactive therapy with those continuing. <bold>Method:</bold> Retrospective data from the Dutch cystic fibrosis registry were used. PwCF starting ETI in 2022 were included. FEV1 percent predicted (FEV1 ppd), exacerbation frequency and use of mucoactive therapy at baseline (BL), 6,12 and 18 months were analyzed. <bold>Result:</bold> 65 adult Pwcf (60% male; 59% homozygous with a dF508 mutation) were included. 44(68%) were using mucoactive inhaled therapy. Compared to BL, FEV1 at 6,12 and 18 months increased significantly (70,8% (±21.6) at BL; 82.65% (±19,4) at 6m; 83.50% (±18.8) at 12m and 84.20% (±19.9) at18 m, p< 0.001). There was a significant decrease in the number of exacerbations. 64% discontinued mucoactive therapy within 18 months. After 18 months, there was no difference in FEV1 and exacerbation frequency in PwCF who discontinued and those who continued mucoactive therapy. <bold>Conclusion:</bold> PwCF started on ETI showed a significant improvement in FEV1 ppd and a reduced exacerbation frequency and this effect was continued at 6, 12 and 18 months. Discontinuation of mucoactive treatment was not associated with a reduced treatment response. These results may indicate that some PwCF could safely discontinue inhaled mucoactive therapy after start of ETI.