Please use this identifier to cite or link to this item: https://dora.health.qld.gov.au/qldresearchjspui/handle/1/3583
Title: Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for phe508del CFTR
Authors: Munck, A.
Wainwright, Claire 
Elborn, J. S.
Ramsey, B. W.
Marigowda, G.
Huang, X.
Cipolli, M.
Colombo, C.
Davies, J. C.
De Boeck, K.
Flume, P. A.
Ratjen, F.
Boyle, M. P.
Waltz, D.
Rowe, S. M.
Konstan, M. W.
McColley, S. A.
McCoy, K.
McKone, E. F.
Issue Date: 2015
Source: 373, (3), 2015, p. 220-231
Pages: 220-231
Journal: New England Journal of Medicine
Abstract: BACKGROUND: Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation. METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24. RESULTS: A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo. CONCLUSIONS: These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation.L6052079202015-07-21
2015-07-23
DOI: 10.1056/NEJMoa1409547
Resources: https://www.embase.com/search/results?subaction=viewrecord&id=L605207920&from=exporthttp://dx.doi.org/10.1056/NEJMoa1409547 |
Keywords: hemoptysis;homozygosity;human;hypertransaminasemia;lung disease;male;middle aged;molecular pathology;nausea;nose obstruction;oropharynx pain;outcome assessment;phase 3 clinical trial;prediction;predictive value;priority journal;randomized controlled trial;rash;rhinopharyngitis;school child;upper respiratory tract infection;vx 770;vx 809;syndrome;NCT01807923NCT01807949;cystic fibrosis transmembrane conductance regulator;ivacaftor;lumacaftor;placebo;adult;article;bronchospasm;chest tightness;child;clinical effectiveness;controlled study;coughing;cystic fibrosis;cystic fibrosis transmembrane conductance regulator gene;diarrhea;disease exacerbation;distal intestinal obstruction syndrome;double blind procedure;drug efficacy;drug fatality;drug response;drug safety;drug tolerability;drug withdrawal;dyspnea;female;forced expiratory volume;gene;gene mutation;headache
Type: Article
Appears in Sites:Children's Health Queensland Publications

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