title: Efficacy response in CF patients treated with ivacaftor: post-hoc analysis.
abstract: Clinical studies in patients with cystic fibrosis and G551D-CFTR showed that the group treated with ivacaftor had improved clinical outcomes. To better understand the effect of ivacaftor therapy across the distribution of individual FEV(1) responses, data from Phase 3 studies (STRIVE/ENVISION) were re-examined. In this post-hoc analysis of patients (n = 209) who received 48 weeks of ivacaftor or placebo, patients were assigned to tertiles according to FEV(1) response. These groups were then used to evaluate response (FEV(1), sweat chloride, weight, CFQ-R, and pulmonary exacerbation). The number needed to treat (NNT) was calculated for specific thresholds for each outcome. Across all tertiles, numerical improvements in FEV(1), sweat chloride, CFQ-R and the frequency of pulmonary exacerbations were observed in ivacaftor-treated patients: the treatment difference versus placebo was statistically significant for all outcomes in the upper tertile and for some outcomes in the lower and middle tertiles. The NNT for a ≥ 5% improvement in %predicted FEV(1) was 1.90, for a ≥ 5% body weight increase was 5.74, and to prevent a pulmonary exacerbation was 3.85. This analysis suggests that the majority of patients with clinical characteristics similar to STRIVE/ENVISION patients have the potential to benefit from ivacaftor therapy.
authors.affiliation: 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
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Plant
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.forename: Sally
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Anne
authors.initials: A
authors.lastname: Munck
authors.forename: Richard
authors.initials: R
authors.lastname: Ahrens
authors.forename: Charles
authors.initials: C
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D000627:Aminophenols / Q000627:therapeutic use*; D002648:Child; D002712:Chlorides / Q000032:analysis; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D009154:Mutation; D061366:Numbers Needed To Treat; D015363:Quinolones / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D013542:Sweat / Q000737:chemistry; D015430:Weight Gain; D055815:Young Adult
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D002712:Chlorides; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR; clinical response; cystic fibrosis; ivacaftor