Dataset Information

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1.

ABSTRACT: BACKGROUND:Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement. METHODS:Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1?s (ppFEV1) change from baseline to day 15 into threshold categories (absolute change ?0 vs >0; relative change <5% vs ?5%) and compared PEx rates vs placebo. RESULTS:LUM (400?mg q12h)/IVA (250?mg q12h)-treated patients (n?=?369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV1?>?0 and 0.85 for those with absolute change ?0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40-0.69; P?

SUBMITTER: McColley SA

PROVIDER: S-EPMC6629021 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV<sub>1</sub>.

McColley Susanna A SA Konstan Michael W MW Ramsey Bonnie W BW Stuart Elborn J J Boyle Michael P MP Wainwright Claire E CE Waltz David D Vera-Llonch Montserrat M Marigowda Gautham G Jiang John G JG Rubin Jaime L JL

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20180823 1

<h4>Background</h4>Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement.<h4>Methods</h4>Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV<sub>1</sub>) change from baseline ...[more]

PMID: 30146268

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Project description: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.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.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.These data show that lumacaftor in combination with ivacaftor provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.).

Dataset Information

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV1.

Publications

Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV<sub>1</sub>.

Similar Datasets

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