Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor

Dig Dis Sci. 2016 Jan;61(1):198-207. doi: 10.1007/s10620-015-3834-2. Epub 2015 Aug 7.

Abstract

Background: 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.

Aim: 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.

Methods: 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).

Results: 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/m(2) (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.

Conclusions: Nutritional status improved following treatment with ivacaftor for 48 weeks.

Keywords: Bicarbonate; Cystic fibrosis transmembrane conductance regulator; Growth; Kalydeco; Potentiator; Weight gain.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aminophenols / administration & dosage*
  • Child
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / agonists*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Membrane Transport Modulators / administration & dosage*
  • Mutation*
  • Nutritional Status / drug effects*
  • Phenotype
  • Quinolones / administration & dosage*
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Weight Gain / drug effects*
  • Young Adult

Substances

  • Aminophenols
  • CFTR protein, human
  • Membrane Transport Modulators
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor