Universität zu Köln

Rowe, Steven M., McColley, Susanna A., Rietschel, Ernst, Li, Xiaolei, Bell, Scott C., Konstan, Michael W., Marigowda, Gautham, Waltz, David and Boyle, Michael P. (2017). Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR. Ann. Am. Thoracic Society, 14 (2). S. 213 - 220. NEW YORK: AMER THORACIC SOC. ISSN 2325-6621

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Abstract

Rationale: In a prior study, lumacaftor/ivacaftor treatment (<= 28 d) in patients with cystic fibrosis (CF) heterozygous for F508del-CFTR did not improve lung function. Objectives: To evaluate an optimized lumacaftor/ivacaftor dosing regimen with a longer duration in a cohort of patients heterozygous for F508del-CFTR. Methods: Patients aged 18 years or older with a confirmed CF diagnosis and percent predicted FEV1 (ppFEV(1)) of 40 to 90 were randomized to lumacaftor/ivacaftor (400 mg/250 mg every 12 h) or placebo daily for 56 days. Primary outcomes were change in ppFEV(1) at Day 56 and safety. Other disease markers were evaluated. Measurements and Main Results: Of 126 patients, 119 (94.4%) completed the study. Lumacaftor/ivacaftor was well tolerated, although chest tightness and dyspnea occurred more frequently with active treatment than with placebo (27.4% vs. 14.3% and 14.5% vs. 6.3%, respectively). Mean (SD) ppFEV(1) values at baseline were 62.9 (14.3) in the active treatment group and 60.1 (14.0) in the placebo group. Absolute changes in ppFEV(1) (least squares mean [SE]) at Day 56 were -0.6 (0.8) percentage points in the active treatment group and -1.2 (0.8) percentage points in the placebo group (P = 0.60). CF respiratory symptom scores in the active treatment group improved by a mean of 5.7 points versus a decrease of -0.8 in the placebo group (P < 0.01). No changes in body mass index occurred. Changes from baseline in sweat chloride (least squares mean [SE]) at Day 56 were -11.8 (1.3) mmol/L in the active treatment group and -0.8 (1.2) mmol/L in the placebo group (P < 0.0001). Conclusions: Sweat chloride and respiratory symptom scores improved with lumacaftor/ivacaftor, though no meaningful benefit was seen in ppFEV(1) or body mass index in patients heterozygous for F508del-CFTR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rowe, Steven M. UNSPECIFIED UNSPECIFIED UNSPECIFIED McColley, Susanna A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Xiaolei UNSPECIFIED UNSPECIFIED UNSPECIFIED Bell, Scott C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Konstan, Michael W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marigowda, Gautham UNSPECIFIED UNSPECIFIED UNSPECIFIED Waltz, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyle, Michael P. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-241517
DOI:	10.1513/AnnalsATS.201609-689OC
Journal or Publication Title:	Ann. Am. Thoracic Society
Volume:	14
Number:	2
Page Range:	S. 213 - 220
Date:	2017
Publisher:	AMER THORACIC SOC
Place of Publication:	NEW YORK
ISSN:	2325-6621
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POTENTIATOR IVACAFTOR; CFTR POTENTIATOR; PHE508DEL CFTR; IN-VITRO; MUTATION; RESCUE Multiple languages Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24151