Does changing from lumacaftor/ivacaftor (Orkambi) to tezacaftor/ivacaftor + ivacaftor (Symkevi + ivacaftor) offer any clinical benefits in children with cystic fibrosis (CF)?

ABSTRACT

From September 2020 until January 2022, children with CF in the UK aged 6–12 years homozygous for F508del had a choice of CFTR modulators Lumacaftor/ivacaftor(LUM/IVA) or tezacaftor/ivacaftor (TEZ/IVA)+ ivacaftor (IVA). Although benefit of the individual agents has been demonstrated in clinical trials, there is no direct comparison between treatments.1 Objectives: Review of Forced Expiratory Volume in 1 second (FEV1) and nutritional clinical benefits of switching from LUM/IVA to TEZ/IVA + IVA. Method: A retrospective review of 18 paediatric patients (pts) swapped from LUM/IVA to TEZ/IVA + IVA. Data collected of length of time on each CFTR modulator, body mass index (BMI) centile, FEV1 (% predicted and zscore). FEV1 data analysed using ANOVA test. Results: 12 female;6 male pts (Mean age 9 yrs 6mths (range 8–12 years)). Two pts swapped from LUM/IVA due to tolerability issues. The other families chose to swap. Mean length of time was 13 mths (±1.3) on LUM/IVA and 9mths ± 1.2 on TEZ/IVA + IVA. Spirometry;table 1 (Table Presented) Conclusion: Swapping CFTR modulators for most pts offered no clear improvement in FEV1 or BMI, the surrogate markers of lung and nutritional health. However, pts did not experience the usual decline in FEV1 seen in CF. There are many potential confounding factors that need to be considered, including that data was collected during the COVID pandemic. As new modulators are developed, further research will be required to better understand their mechanism of action in individual pts to guide optimal personalised prescribing. 1 Walker S., et al., A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11years with cystic fibrosis, J CYST FIBROS;June 2019;18(708–713).