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 R 2 = 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.
Bibliographical noteFunding Information:
Supported by Vertex Pharmaceuticals, Inc, The National Center for Advancing Translational Sciences, National Institutes of Health (UL1TR001878), the Clinical Translational Research Center (UL1RR024134, UL1TR000003), Nutrition Center, and the Cortner Endowed Chair (VAS) at Children's Hospital of Philadelphia. The study sponsor, Vertex Pharmaceuticals, Inc, had no involvement in the study design, the collection, analysis and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. The malabsorption blood test patent invented by V.S. is held by Children's Hospital of Philadelphia and the test is not licensed commercially. All other authors declare no conflicts of interest.
© 2018 Elsevier Inc.
- cystic fibrosis
- energy expenditure
- fat absorption
- gut inflammation