Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor
- 893 Downloads
The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gating mutation G551D prevents sufficient ion transport due to reduced channel-open probability. Ivacaftor, an oral CFTR potentiator, increases the channel-open probability.
To further analyze improvements in weight and body mass index (BMI) in two studies of ivacaftor in patients aged ≥6 years with CF and the G551D mutation.
Patients were randomized 1:1 to ivacaftor 150 mg or placebo every 12 h for 48 weeks. Primary end point (lung function) was reported previously. Other outcomes included weight and height measurements and CF Questionnaire-Revised (CFQ-R).
Studies included 213 patients (aged ≤ 20 years, n = 105; aged > 20 years, n = 108). In patients ≤20 years, adjusted mean change from baseline to week 48 in body weight was 4.9 versus 2.2 kg (ivacaftor vs. placebo, p = 0.0008). At week 48, change from baseline in mean weight-for-age z-score was 0.29 versus −0.06 (p < 0.0001); change in mean BMI-for-age z-score was 0.26 versus −0.13 (p < 0.0001). In patients >20 years, adjusted mean change from baseline to week 48 in body weight was 2.7 versus −0.2 kg (p = 0.0003). Mean BMI change at week 48 was 0.9 versus −0.1 kg/m2 (p = 0.0003). There was no linear correlation evident between changes in body weight and improvements in lung function or sweat chloride. Significant CFQ-R improvements were seen in perception of eating, body image, and sense of ability to gain weight.
Nutritional status improved following treatment with ivacaftor for 48 weeks.
KeywordsWeight gain Growth Cystic fibrosis transmembrane conductance regulator Potentiator Bicarbonate Kalydeco
This study was sponsored by Vertex Pharmaceuticals Incorporated.
Compliance with Ethical Standards
Conflict of interest
Barry Lubarsky is an employee of Vertex Pharmaceuticals Incorporated and may own stock or stock options in the company.
No honoraria or other forms of payment were made for authorship of this article. Editorial assistance for this manuscript was provided by Peloton Advantage, Parsippany, NJ, and was funded by Vertex Pharmaceuticals Incorporated.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. As this was a post hoc analysis, no formal patient consent is required.
- 3.Cystic Fibrosis Registry of Ireland 2012 Annual Report. Dublin, Ireland: Cystic Fibrosis Registry of Ireland; 2014.Google Scholar
- 7.Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton H. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc. 2008;108:832–839.PubMedCrossRefGoogle Scholar
- 25.Alaiwa A, Reznikov LR, Gansemer ND, Zabner J, Welsh MJ. pH modulates the antimicrobial activity of beta defensin-3 (BD-3) [abstract 91]. Pediatr Pulmonol. 2013;48:237.Google Scholar
- 32.Davies JC, Robertson S, Green Y, Rosenfeld M. An open-label study of the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2 to 5 years with CF and a CFTR gating mutation: the KIWI study [poster 200] [abstract]. Presented at the Atlanta, GA, October 9–11, 2014, Annual North American Conference of the Cystic Fibrosis Foundation. 2014.Google Scholar