Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data
Top Cited Papers
- 1 October 2015
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 192 (7), 836-842
- https://doi.org/10.1164/rccm.201503-0578oc
Abstract
Rationale: In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population. Objectives: To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation. Methods: A propensity score was used to match patients with CF greater than or equal to 6 years of age who have a G551D mutation and received ivacaftor in clinical trials for up to 144 weeks with data from patients in the U.S. Cystic Fibrosis Foundation Patient Registry who are homozygous for the F508del mutation. Matching was based on variables including age, sex, weight for age, height for age, body mass index for age, % predicted FEV1, and chronic therapies (dornase alfa, inhaled antibiotics, inhaled and oral corticosteroids). Measurements and Main Results: By calculating the annual estimated rate of decline in lung function for G551D patients receiving ivacaftor and comparing it with the rate of decline in lung function for matched F508del control patients, we show that the rate of lung function decline in G551D ivacaftor-treated patients was slower by nearly half. Moreover, treatment with ivacaftor is shown to improve body mass index and weight-for-age z scores for G551D patients over the 3-year analysis period. Conclusions: These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis.This publication has 28 references indexed in Scilit:
- Modifying disease in cystic fibrosisCurrent Opinion in Pulmonary Medicine, 2013
- Assessment of clinical response to ivacaftor with lung clearance index in cystic fibrosis patients with a G551D- CFTR mutation and preserved spirometry: a randomised controlled trialThe Lancet Respiratory Medicine, 2013
- Growth failure in children with cystic fibrosisJournal of Pediatric Endocrinology and Metabolism, 2012
- A CFTR Potentiator in Patients with Cystic Fibrosis and theG551DMutationThe New England Journal of Medicine, 2011
- Design and powering of cystic fibrosis clinical trials using rate of FEV1 decline as an efficacy endpointJournal of Cystic Fibrosis, 2010
- Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770Proceedings of the National Academy of Sciences of the United States of America, 2009
- Jointly modelling the relationship between survival and pulmonary function in cystic fibrosis patientsStatistics in Medicine, 2002
- Longitudinal analysis of pulmonary function decline in patients with cystic fibrosisThe Journal of Pediatrics, 1997
- Identifying Treatments That Halt Progression of Pulmonary Disease in Cystic FibrosisPediatric Research, 1997
- Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNAScience, 1989