title: Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics, University at Buffalo, State University of New York, Women and Children's Hospital of Buffalo, 219 Bryant Street, Buffalo, NY, 14222, USA. dborowitz@upa.chob.edu.
authors.forename: Drucy
authors.initials: D
authors.lastname: Borowitz
authors.affiliation: Department of Medical Affairs, Vertex Pharmaceuticals Incorporated, 50 Northern Avenue, Boston, MA, 02210, USA. barry_lubarsky@vrtx.com.
authors.forename: Barry
authors.initials: B
authors.lastname: Lubarsky
authors.affiliation: Department of Pediatrics, Hadassah University Hospital, Kiryat Hadassah, PO Box 12000, 91120, Jerusalem, Israel. michaelwil@hadassah.org.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilschanski
authors.affiliation: Assistance publique-Hôpitaux de Paris, Hôpital Robert Debré, Paediatric Gastroenterology and Respiratory Department, CF Center, 48 Sérurier Boulevard, 75019, Paris, France. anne.munck@rdb.aphp.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Munck
authors.affiliation: Department of Pediatrics, Gastroenterology/Nutrition (SMD), University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA. dgelfond@upa.chob.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gelfond
authors.affiliation: Department of Pediatrics, Beatrix Children's Hospital, PO Box 30001, 9700 RB, Groningen, Groningen, The Netherlands. f.a.j.a.bodewes@umcg.nl.
authors.forename: Frank
authors.initials: F
authors.lastname: Bodewes
authors.affiliation: Division of Pediatric Gastroenterology, University of Minnesota, 6th Floor East Building 8952C 2450 Riverside Ave, Minneapolis, MN, 55454, USA. schwa005@umn.edu.
authors.forename: Sarah Jane
authors.initials: SJ
authors.lastname: Schwarzenberg
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000627:Aminophenols / Q000008:administration & dosage*; D002648:Child; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D049990:Membrane Transport Modulators / Q000008:administration & dosage*; D009154:Mutation; D009752:Nutritional Status / Q000187:drug effects*; D010641:Phenotype; D015363:Quinolones / Q000008:administration & dosage*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D049990:Membrane Transport Modulators; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: Bicarbonate; Cystic fibrosis transmembrane conductance regulator; Growth; Kalydeco; Potentiator; Weight gain