Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience

- Information on the clinical efficacy of ivacaftor in patients carrying the p.Ser549Arg (S549R) CFTR mutation was sought.
- Sweat chloride decreased in all patients, and reached a normal range in 75%.
- Lung functions improved in all patients treated: FEV1 improved by 22 ± 14%, FVC by 15 ± 16%; and FEF25-75% by 44 ± 34%.
- BMI significantly increased by 10% and there was a significant change in patients' glucose metabolism.
- A reduction in the number of days per year treated with intravenous antibiotics was noted.

BackgroundIvacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse.AimEfficacy of ivacaftor treatment in patients carrying the p.Ser549Arg (S549R) CFTR mutation.MethodsData obtained from CF patients receiving ivacaftor for one year.ResultsEight CF patients, mean age 21 ± 10 years, received ivacaftor. After one year, significant improvement was found in FEV1, increasing from 74% to 88% (p < 0.001), FVC, 89% to 101% (p = 0.019), and FEF25-75, 59%-76% (p = 0.019). Sweat chloride concentration decreased from 116 ± 8 mmol/L to 51 ± 17 mmol/L (p < 0.001), and BMI increased from 20 ± 3 to 22 ± 4 (p = 0.003). Glucose tolerance improved in five patients. There was no significant change in bacterial colonization.ConclusionsIvacaftor therapy resulted in significant clinical improvement in patients carrying the p.Ser549Arg (S549R) CFTR mutation.