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.
journal_name
Am J Respir Crit Care Medauthors
Sawicki GS,McKone EF,Pasta DJ,Millar SJ,Wagener JS,Johnson CA,Konstan MWdoi
10.1164/rccm.201503-0578OCsubject
Has Abstractpub_date
2015-10-01 00:00:00pages
836-42issue
7eissn
1073-449Xissn
1535-4970journal_volume
192pub_type
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