title: Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data.
abstract: BACKGROUND
  In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate comparator population.
  
  
  OBJECTIVE
  To examine, over a 3-year period, whether ivacaftor therapy affects pulmonary function and nutritional measures in patients with CF with a G551D mutation compared with patients with CF who are homozygous for the F508del mutation.
  
  
  METHODS
  A propensity score was used to match patients with CF greater than or equal to 6 years of age who have a G551D mutation and received ivacaftor in clinical trials for up to 144 weeks with data from patients in the U.S. Cystic Fibrosis Foundation Patient Registry who are homozygous for the F508del mutation. Matching was based on variables including age, sex, weight for age, height for age, body mass index for age, % predicted FEV1, and chronic therapies (dornase alfa, inhaled antibiotics, inhaled and oral corticosteroids).
  
  
  RESULTS
  By calculating the annual estimated rate of decline in lung function for G551D patients receiving ivacaftor and comparing it with the rate of decline in lung function for matched F508del control patients, we show that the rate of lung function decline in G551D ivacaftor-treated patients was slower by nearly half. Moreover, treatment with ivacaftor is shown to improve body mass index and weight-for-age z scores for G551D patients over the 3-year analysis period.
  
  
  CONCLUSIONS
  These findings suggest that ivacaftor is a disease-modifying therapy for the treatment of cystic fibrosis.
authors.affiliation: 1 Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Sawicki
authors.affiliation: 2 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Edward F
authors.initials: EF
authors.lastname: McKone
authors.affiliation: 3 ICON Clinical Research, San Francisco, California.
authors.forename: David J
authors.initials: DJ
authors.lastname: Pasta
authors.affiliation: 3 ICON Clinical Research, San Francisco, California.
authors.forename: Stefanie J
authors.initials: SJ
authors.lastname: Millar
authors.affiliation: 4 Vertex Pharmaceuticals Incorporated, Boston, Massachusetts.|5 University of Colorado Medical School, Aurora, Colorado; and.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Wagener
authors.affiliation: 4 Vertex Pharmaceuticals Incorporated, Boston, Massachusetts.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Johnson
authors.affiliation: 6 Case Western Reserve University School of Medicine Rainbow Babies and Children's Hospital, Cleveland, Ohio.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
mesh_terms: D000627:Aminophenols / Q000494:pharmacology / Q000627:therapeutic use*; D015992:Body Mass Index; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D009752:Nutritional Status; D057216:Propensity Score; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D012042:Registries; D012129:Respiratory Function Tests
chemical_list: D000627:Aminophenols; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR; cystic fibrosis; disease modification; ivacaftor; lung function decline