Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries

J Cyst Fibros. 2020 Jan;19(1):68-79. doi: 10.1016/j.jcf.2019.05.015. Epub 2019 Jun 10.


Background: Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5 years.

Methods: Data from existing US and UK CF patient registries were used to assess longitudinal patterns in lung function, nutritional status, pulmonary exacerbations and hospitalizations, CF-related diabetes (CFRD), and Pseudomonas aeruginosa in ivacaftor-treated vs untreated comparator cohorts matched by age, sex, and disease severity.

Results: US analyses included 635 ivacaftor-treated patients and 1874 comparators followed for 5 years from year 1 of market availability (2012-2016). Evaluation of outcome patterns from pretreatment baseline (2011) through year 5 (2016), showed that relative to comparators, ivacaftor-treated patients had better preserved lung function (mean change in percent predicted FEV1, -0.7 percentage points with ivacaftor vs -8.3 percentage points in comparators) and improved nutritional status (mean body mass index change +2.4 kg/m2 with ivacaftor vs +1.6 kg/m2 in comparators). US patients treated with ivacaftor had significantly lower frequencies of exacerbations and hospitalizations in each of the 5 years of follow-up relative to pretreatment baseline and comparators. Favorable trends in CFRD and P. aeruginosa prevalence were also observed. Findings from the smaller UK registry were directionally similar to and consistent with US findings.

Conclusions: This observational study represents the largest longitudinal analysis of patients treated with ivacaftor in a real-world setting. The findings support disease modification by CFTR modulation with ivacaftor.

Keywords: CF complications; CF disease progression; CFTR; CFTR modulator; Ivacaftor.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminophenols / therapeutic use*
  • Chloride Channel Agonists / therapeutic use
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / epidemiology
  • Cystic Fibrosis* / microbiology
  • Cystic Fibrosis* / physiopathology
  • Disease Progression*
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Longitudinal Studies
  • Male
  • Pseudomonas aeruginosa / isolation & purification*
  • Quinolones / therapeutic use*
  • Registries / statistics & numerical data
  • Respiratory Function Tests* / methods
  • Respiratory Function Tests* / statistics & numerical data
  • United Kingdom / epidemiology
  • United States / epidemiology


  • Aminophenols
  • Chloride Channel Agonists
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor