Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations.

Abstract

OBJECTIVE:

To determine if ivacaftor treatment results in weight gain and improved pulmonary function in people with cystic fibrosis transmembrane conductance regulator gating mutations.

STUDY DESIGN:

Children and adults with cystic fibrosis and at least 1 cystic fibrosis transmembrane conductance regulator gating mutation were evaluated in this observational study before and after 3 months of ivacaftor treatment. Body size and composition, total energy expenditure, resting energy expenditure (REE%) as percent predicted, coefficient of fat absorption (CFA%), fecal calprotectin, fecal elastase, and quality of life were assessed. Some outcomes were explored by pancreatic status.

RESULTS:

There were 23 patients (5-61 years of age) who completed the study; 70% had pancreatic insufficiency (PI). Patients gained 2.5 ± 2.2 kg (P < .001) with increased (P < .05) fat-free mass (0.9 ± 1.9 kg) and fat mass (1.6 ± 1.5 kg). REE% decreased by 5.5 ± 12.0% (P < .05), fecal calprotectin decreased by 30 ± 40 µg/g stool (P < .01), and total energy expenditure was unchanged. Improvements were greater for PI than patients who were pancreatic-sufficient. CFA% increased significantly only with PI. The change (Δ) in weight was positively correlated with the percent change in forced expiratory volume at 1 second (r = 0.46; P = .028) and ΔCFA% (r = 0.47; P = .032) and negatively with ΔREE% (r = -0.50; P = .017). Together, ΔREE%, ΔCFA%, and the percent change in forced expiratory volume at 1 second explained 58% of the variance in weight gain (adjusted R2 = 0.579; P = .0007). Growth status and muscle strength improved, as did quality of life in several domains. Fecal elastase increased in most patients with pancreatic sufficiency, with no change in those with PI.

CONCLUSIONS:

Mechanisms identified for ivacaftor-associated weight gain were decreased REE, gut inflammation, and fat malabsorption (CFA).

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT02141464.

• Authors: Virginia A Stallings, Nina Sainath, Megan Oberle, Chiara Bertolaso, Joan I Schall
• Journal: The Journal of pediatrics (J Pediatr) Vol. 201 Pg. 229-237.e4 (10 2018) ISSN: 1097-6833 [Electronic] United States
• PMID: 30029855 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Aminophenols
• CFTR protein, human
• Chloride Channel Agonists
• Quinolones
• Cystic Fibrosis Transmembrane Conductance Regulator
• ivacaftor
• DNA

Topics

• Adolescent
• Adult
• Aminophenols (therapeutic use)
• Child
• Child, Preschool
• Chloride Channel Agonists (therapeutic use)
• Cystic Fibrosis (drug therapy, genetics, metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (genetics, metabolism)
• DNA (genetics)
• DNA Mutational Analysis
• Energy Metabolism (physiology)
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Quality of Life
• Quinolones (therapeutic use)
• Treatment Outcome
• Weight Gain (physiology)
• Young Adult