Aims In clinical trials, Kaftrio (ivacaftor/tezacaftor/elexacaftor) has shown significant improvement in clinically important parameters in children with cystic fibrosis (cwCF) including a reduction in sweat chloride levels.¹ In our study we aimed to check the effect of Kaftrio on sweat chloride levels in cwCF in real-world clinical practice.

Method Data of cwCF (aged 6–18 years) who received Kaftrio from 2020 to 2023 was collected retrospectively using the electronic patient record system. All children had sweat tests performed after starting Kaftrio and sweat chloride levels were compared with pre-Kaftrio levels.

Results 31 cwCF received Kaftrio between 2020–2023. 17 were homozygous for F508del and 14 heterozygous. 96.8% of cwCF on Kaftrio (30/31) had a reduced level of sweat chloride concentration post-therapy. Concordance issues with Kaftrio were identified in one non-responder child and once addressed, sweat chloride levels did reduce on repeat sweat tests. The mean reduction in sweat chloride levels was 56.7 mmol/L. 58% (18/31) had normal sweat chloride concentration (<40 mmol/L) on the repeat test post Kaftrio. 9 cwCF had intermediate sweat chloride level (40–59 mmol/L) and only 4 cwCF had abnormal levels (≥60 mmol/L). Homozygous children showed a mean reduction of 60.2 mmol/L in sweat chloride levels in contrast to a mean reduction of 54.9 mmol/L in heterozygous children.

Conclusion In our real-world clinical practice experience, the use of Kaftrio in cwCF resulted in a significant reduction in sweat chloride levels. Post Kaftrio, sweat chloride levels were in the normal range (<40 mmol/L) in more than half of the participants. Children homozygous for F508del showed a greater reduction in sweat chloride levels when compared to those heterozygous for F508del. These results are similar to the results seen in clinical trials. In our experience compliance with the treatment was the single most important factor identified for non-response to Kaftrio.

Reference

1. Heijerman HG, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial. Lancet. 2019;394(10212):1940–1948.