The development of ivacaftor represents a significant advance in therapeutics for cystic fibrosis (CF) patients with the G551D mutation. Patients with an FEV1<40% predicted represent a significant proportion of eligible patients but were excluded from phase III clinical trials and the effectiveness of the drug in this population is therefore unknown.
Data were collected from adult CF centres in the UK and Ireland with patients enrolled in an ivacaftor compassionate use programme (FEV1<40% or on lung transplant waiting list). Clinically recorded data were collated from patient records for 1 year prior, and for a period of 90 to 270 days following ivacaftor commencement. Each patient was matched with up to two controls who would have met the requirements for the compassionate use programme with the exception of genotype.
21 patients received ivacaftor for a median of 237 days. Mean FEV1 improved from 26·5% to 30·7% predicted (p=0·01), representing a 16.7% relative improvement. Median weight improved from 49·8 to 51·6kg (p=0·006). Median in-patient intravenous antibiotic days declined from 23 to 0 days per year (p=0.001) and median total intravenous treatment days decreased from 74 to 38 days per year (p=0.002) following ivacaftor. Changes in pulmonary function and intravenous antibiotic requirements were significant compared to control subjects.
Ivacaftor was clinically effective in CF patients carrying the G551D mutation with severe pulmonary disease. The reductions in treatment requirements were clinically and statistically significant and have not been described in less severe populations.