Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study

Abstract

Vertex Pharmaceuticals Incorporated.

Ivacaftor for cystic fibrosis

“…The evidence for effectiveness of ivacaftor is drawn from small, double blind, randomised controlled trials and observational post-licensing studies678910 in which this drug was given as an add-on therapy to ongoing medications in patients with cystic fibrosis and the genotype Gly551Asp. Table 1 presents the results of these studies (see also fig 2).…”

Cystic Fibrosis

“…The drug has been shown in randomized and controlled trials to significantly improve pulmonary function (FEV 1 % pred absolute change: + 10.6% [33]), body weight (+ 2.8 kg [33]), and the quality of life, and also to reduce infectious exacerbations (− 55 % [33]) and lower the chloride level in sweat (− 47.9 mmol/L [33]; a direct indication of improved CFTR function), when it is given for 24 weeks to patients over age 6 who have at least one so-called gating mutation (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R) (33,34). For patients aged 2 to 6, a body-weight-adapted granulate has been found to be safe and to lower the chloride level in sweat (35). Ivacaftor has been approved for patients aged 18 and above with the R117H mutation.…”

Diagnosis and early life risk factors for bronchiectasis in cystic fibrosis: a review

“…Reports are increasing on the beneficial effects of improving CFTR function on various aspects of the CF phenotype [44][45][46][47][48]. There is even a report of improvement in Brody score in patients with established structural lung disease [49].…”