Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor

Abstract

BackgroundIvacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers.ObjectiveThis ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability.MethodsAnnual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here.ResultsAnalyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function.ConclusionsWhile general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of literature supporting disease modification by CFTR modulation with ivacaftor.EU PAS registration numberEUPAS4270

Cystic fibrosis year in review 2018, part 1

“…Reductions in CF‐related diabetes and improved measures of bone health were seen in the US CFFPR/UK CFR, but not in the French CF Registry . The US CFFPR/UK CFR demonstrated reductions in hepatobiliary complications but not gastrointestinal or pulmonary complications . Rates of depression were lower in the ivacaftor‐treated patients in the US, but similar in those in the UK .…”

“…Rates of CF‐related complications varied between these studies. Reductions in CF‐related diabetes and improved measures of bone health were seen in the US CFFPR/UK CFR, but not in the French CF Registry . The US CFFPR/UK CFR demonstrated reductions in hepatobiliary complications but not gastrointestinal or pulmonary complications .…”

“…The US CFFPR/UK CFR demonstrated reductions in hepatobiliary complications but not gastrointestinal or pulmonary complications . Rates of depression were lower in the ivacaftor‐treated patients in the US, but similar in those in the UK . Risk of death was reduced from 1.6% to 0.6% and transplantation from 1.1% to 0.2% in the US/UK evaluation …”

“…Analyses of long‐term outcomes from registries around the globe gives further insight into modulator effects. Data from 80 patients in the CF Registry of Ireland, 1256 patients in the US CFFPR combined with 411 patients in the UK CF Registry, 57 patients in the French CF Registry, and a single center evaluation in 33 patients from Cork, Ireland shared outcomes for 1 to 3 years post ivacaftor approval in patients with a G551D mutation. Only the study using the CFFPR and UK CF Registry also included patients with other gating mutations in their analysis.…”

“…Methodology differed; the Cork study was prospective, and the others retrospective analyses of prospectively collected data. Both the French and Irish CF Registry Studies compared pre and post ivacaftor use in patients, while the CFF PR and UK CFR compared those on ivacaftor to matched comparators for age, sex, and CFTR genotype severity, not on ivacaftor. The studies showed consistently favorable outcomes in FEV1pp, BMI, sweat chloride values, use of IV and oral antibiotics, and hospitalizations for pulmonary exacerbations.…”