Imperial College London
Alternate

ProfessorJaneDavies

Faculty of Medicine, National Heart & Lung Institute

Professor of Paediatric Respirology & Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7973j.c.davies

 
 
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Assistant

 

Mrs Gina Rivellini +44 (0)20 7594 7986

 
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Location

 

G44Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wainwright:2015:10.1056/NEJMoa1409547,
author = {Wainwright, CE and Elborn, JS and Ramsey, BW and Marigowda, G and Huang, X and Cipolli, M and Colombo, C and Davies, JC and De, Boeck K and Flume, PA and Konstan, MW and McColley, SA and Mccoy, K and McKone, EF and Munck, A and Ratjen, F and Rowe, SM and Waltz, D and Boyle, MP},
doi = {10.1056/NEJMoa1409547},
journal = {New England Journal of Medicine},
pages = {220--231},
title = {Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR},
url = {http://dx.doi.org/10.1056/NEJMoa1409547},
volume = {373},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUNDCystic 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.METHODSWe 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.RESULTSA 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
AU  - Wainwright,CE
AU  - Elborn,JS
AU  - Ramsey,BW
AU  - Marigowda,G
AU  - Huang,X
AU  - Cipolli,M
AU  - Colombo,C
AU  - Davies,JC
AU  - De,Boeck K
AU  - Flume,PA
AU  - Konstan,MW
AU  - McColley,SA
AU  - Mccoy,K
AU  - McKone,EF
AU  - Munck,A
AU  - Ratjen,F
AU  - Rowe,SM
AU  - Waltz,D
AU  - Boyle,MP
DO  - 10.1056/NEJMoa1409547
EP  - 231
PY  - 2015///
SN  - 1533-4406
SP  - 220
TI  - Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR
T2  - New England Journal of Medicine
UR  - http://dx.doi.org/10.1056/NEJMoa1409547
UR  - https://www.nejm.org/doi/10.1056/NEJMoa1409547
UR  - http://hdl.handle.net/10044/1/37072
VL  - 373
ER  -
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