{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:29:56Z","timestamp":1789597796791,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T00:00:00Z","timestamp":1689206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold>Ivacaftor, the first CFTR modulator drug, leads to significant long-term improvement in lung function and weight gain. The mechanism as well as the long-term impact of ivacaftor on weight, resting energy expenditure (REE) and body composition remains to be explored.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>This prospective observational study included 18 people with CF (pwCF) (age: median (range) 20 (6\u201358) years) carrying at least one CFTR gating mutation commencing ivacaftor. Assessments of body composition, REE and laboratory investigations were performed at baseline and 6, 12 and 24 months after treatment initiation.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>Treatment with ivacaftor was associated with a significantly positive change in BMI z-score at 24 months. Fat mass (mean (95% CL) of 6.5\u00a0kg (4.0; 9.0) from baseline,<jats:italic>p<\/jats:italic>= 0.0001), but not fat-free mass changed under ivacaftor treatment. There was a significant positive correlation between weight and fat mass change. Overall, there was no significant change in measured REE from baseline (mean (95% CL) of 108\u00a0kcal\/d (\u221212; 228),<jats:italic>p<\/jats:italic>= 0.07) in our cohort. Pancreatic function and other nutritional markers did not change with treatment, with the exception of an increase in serum vitamin A levels (<jats:italic>p<\/jats:italic>= 0.006).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>The weight gain observed in ivacaftor treated pwCF is predominantly secondary to increases in fat mass warranting early counseling of people starting on CFTR-modulating treatment with respect to healthy diet and physical exercise.<\/jats:p>","DOI":"10.3389\/fphar.2023.1157459","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T10:40:52Z","timestamp":1689244852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Weight increase in people with cystic fibrosis on CFTR modulator therapy is mainly due to increase in fat mass"],"prefix":"10.3389","volume":"14","author":[{"given":"Marialena","family":"Mouzaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Dupuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Avolio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Ratjen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tullis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Gonska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1359\/JBMR.051023","article-title":"BMD and body composition in children and young patients affected by cystic fibrosis","volume":"21","author":"Bianchi","year":"2006","journal-title":"J. Bone Min. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1007\/s10620-015-3834-2","article-title":"Nutritional status improved in cystic fibrosis patients with the G551D mutation after treatment with ivacaftor","volume":"61","author":"Borowitz","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/jhn.12252","article-title":"Sex and age-related differences in perceived, desired and measured percentage body fat among adults","volume":"28","author":"Campisi","year":"2015","journal-title":"J. Hum. Nutr. Diet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6900","DOI":"10.3390\/jcm11236900","article-title":"Cystic Fibrosis Patients with F508del\/Minimal Function Genotype: Laboratory and Nutritional Evaluations after One Year of Elexacaftor\/Tezacaftor\/Ivacaftor Treatment","volume":"11","author":"Carnovale","year":"2022","journal-title":"J. Clin. Med."},{"key":"B5","first-page":"1","article-title":"Report of a joint FAO\/WHO\/UNU expert consultation","volume":"724","year":"1985","journal-title":"World Health Organ Tech. Rep. Ser."},{"key":"B6","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/s0022-3476(05)83042-2","article-title":"The cystic fibrosis gene and resting energy expenditure","volume":"119","author":"Fried","year":"1991","journal-title":"J. Pediatr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e81","DOI":"10.1038\/ctg.2017.10","article-title":"Impact of CFTR modulation on intestinal pH, motility, and clinical outcomes in patients with cystic fibrosis and the G551D mutation","volume":"8","author":"Gelfond","year":"2017","journal-title":"Clin. Transl. Gastroenterol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.jcf.2021.09.010","article-title":"CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis","volume":"21","author":"Gould","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"B9","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1007\/s00198-011-1649-3","article-title":"Adiposity and bone health in Spanish adolescents. The HELENA study","volume":"23","author":"Gracia-Marco","year":"2012","journal-title":"Osteoporos. Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1164\/rccm.201609-1954OC","article-title":"Restoring cystic fibrosis transmembrane conductance regulator function reduces airway bacteria and inflammation in people with cystic fibrosis and chronic lung infections","volume":"195","author":"Hisert","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1164\/ajrccm.165.4.2104065","article-title":"Pulmonary function, body composition, and protein catabolism in adults with cystic fibrosis","volume":"165","author":"Ionescu","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/ijpo.242","article-title":"Diagnostic performance of body mass index to identify obesity as defined by body adiposity in children and adolescents: A systematic review and meta-analysis","volume":"10","author":"Javed","year":"2015","journal-title":"Pediatr. Obes."},{"key":"B13","doi-asserted-by":"publisher","first-page":"111124","DOI":"10.1016\/j.nut.2020.111124","article-title":"Body composition and weight changes after ivacaftor treatment in adults with cystic fibrosis carrying the G551 D cystic fibrosis transmembrane conductance regulator mutation: A double-blind, placebo-controlled, randomized, crossover study with open-label extension","volume":"85","author":"King","year":"2021","journal-title":"Nutrition"},{"key":"B14","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/s0022-3476(85)80130-x","article-title":"Effects of long-term nutritional rehabilitation on body composition and clinical status in malnourished children and adolescents with cystic fibrosis","volume":"107","author":"Levy","year":"1985","journal-title":"J. Pediatr."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1378\/chest.103.6.1819","article-title":"Resting energy expenditure. Evolution during antibiotic treatment for pulmonary exacerbation in cystic fibrosis","volume":"103","author":"Naon","year":"1993","journal-title":"Chest"},{"key":"B16","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1093\/ajcn\/52.2.209","article-title":"Body composition of adult cystic fibrosis patients and control subjects as determined by densitometry, bioelectrical impedance, total-body electrical conductivity, skinfold measurements, and deuterium oxide dilution","volume":"52","author":"Newby","year":"1990","journal-title":"Am. J. Clin. Nutr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"17834","DOI":"10.1038\/s41598-018-36364-6","article-title":"Impact of CFTR modulation with ivacaftor on gut microbiota and intestinal inflammation","volume":"8","author":"Ooi","year":"2018","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1054\/clnu.1999.0079","article-title":"Pathogenesis of malnutrition in cystic fibrosis, and its treatment","volume":"19","author":"Pencharz","year":"2000","journal-title":"Clin. Nutr."},{"key":"B19","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3233\/PRM-160377","article-title":"The measurement of body composition in children with spina bifida: Feasibility and preliminary findings","volume":"9","author":"Polfuss","year":"2016","journal-title":"J. Pediatr. Rehabil. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3-95-yr age range: The global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur. Respir. J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","article-title":"A CFTR potentiator in patients with cystic fibrosis and the G551D mutation","volume":"365","author":"Ramsey","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1378\/chest.12-0628","article-title":"Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa","volume":"142","author":"Ratjen","year":"2012","journal-title":"Chest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fped.2014.00033","article-title":"Body composition and pulmonary function in cystic fibrosis","volume":"2","author":"Sheikh","year":"2014","journal-title":"Front. Pediatr."},{"key":"B25","doi-asserted-by":"publisher","first-page":"S101","DOI":"10.1016\/s1569-1993(16)30437-4","article-title":"198 3-month ivacaftor (Kalydeco\u2122) treatment resulted in weight gain, decreased resting energy expenditure and gut inflammation, and increased pulmonary function, muscle mass and strength, and growth status","volume":"15","author":"Stallings","year":"2016","journal-title":"J. Cyst. Fibros. official J. Eur. Cyst. Fibros. Soc."},{"key":"B26","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jpeds.2018.05.018","article-title":"Energy balance and mechanisms of weight gain with ivacaftor treatment of cystic fibrosis gating mutations","volume":"201","author":"Stallings","year":"2018","journal-title":"J. Pediatr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1513\/AnnalsATS.201501-021FR","article-title":"Multiple-breath washout as a lung function test in cystic fibrosis. A cystic fibrosis foundation workshop report","volume":"12","author":"Subbarao","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.70252\/RJLG4539","article-title":"Comparison of body composition measurements using a new caliper, two established calipers, hydrostatic weighing, and BodPod","volume":"2","author":"Talbert","year":"2009","journal-title":"Int. J. Exerc Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"S50","DOI":"10.1016\/s1569-1993(15)30162-4","article-title":"ePS05.3 Ivacaftor and its effects on body composition in adults with G551D related cystic fibrosis","volume":"14","author":"Tierney","year":"2015","journal-title":"J. Cyst. Fibros."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1157459\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T02:26:46Z","timestamp":1729736806000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1157459\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,13]]},"references-count":28,"alternative-id":["10.3389\/fphar.2023.1157459"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1157459","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,13]]},"article-number":"1157459"}}