Lumacaftor/Ivacaftor reduces pulmonary exacerbations in patients irrespective of initial changes in FEV 1

J Cyst Fibros. 2019 Jan;18(1):94-101. doi: 10.1016/j.jcf.2018.07.011. Epub 2018 Aug 23.

Abstract

Background: Improved lung function and fewer pulmonary exacerbations (PEx) were observed with lumacaftor/ivacaftor (LUM/IVA) in patients with cystic fibrosis homozygous for F508del. It is unknown whether PEx reduction extends to patients without early lung function improvement.

Methods: Post hoc analyses of pooled phase 3 data (NCT01807923, NCT01807949) categorized LUM/IVA-treated patients by percent predicted forced expiratory volume in 1 s (ppFEV1) change from baseline to day 15 into threshold categories (absolute change ≤0 vs >0; relative change <5% vs ≥5%) and compared PEx rates vs placebo.

Results: LUM (400 mg q12h)/IVA (250 mg q12h)-treated patients (n = 369) experienced significantly fewer PEx vs placebo, regardless of threshold category. With LUM/IVA, PEx rate per patient per year was 0.60 for those with absolute change in ppFEV1 > 0 and 0.85 for those with absolute change ≤0 (respective rate ratios vs placebo [95% CI]: 0.53 [0.40-0.69; P < .0001], 0.74 [0.55-0.99; P = .04]).

Conclusions: LUM/IVA significantly reduced PEx, even in patients without early lung function improvement.

Keywords: Cystic fibrosis; Ivacaftor; Lumacaftor; Percent predicted forced expiratory volume in 1 s; Pulmonary exacerbations.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aminophenols / therapeutic use*
  • Aminopyridines / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Child
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Disease Progression
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology*
  • Humans
  • Lung / drug effects
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Quinolones / therapeutic use*
  • Respiratory Function Tests
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Drug Combinations
  • Quinolones
  • lumacaftor, ivacaftor drug combination

Associated data

  • ClinicalTrials.gov/NCT01807923
  • ClinicalTrials.gov/NCT01807949