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

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 P P P 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.