An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor

Ann Am Thorac Soc. 2017 Nov;14(11):1662-1666. doi: 10.1513/AnnalsATS.201701-058OC.


Rationale: In July 2015, the U.S. Food and Drug Administration approved lumacaftor/ivacaftor for use in patients with cystic fibrosis (CF). This drug targets the primary defect in the CFTR protein that is conferred by the F508del CFTR mutation.

Objective: As there is limited experience with this therapy outside of clinical trials, this study aims to examine the clinical experience of this new drug in a population with CF.

Results: Retrospective cohort study of individuals followed at the Johns Hopkins CF Center who initiated treatment with lumacaftor/ivacaftor. Patients were followed from 1 year before drug initiation to up to 11 months postinitiation. Key exclusion criteria include previous exposure to lumacaftor/ivacaftor through participation in a clinical trial. Of 116 individuals identified who started lumacaftor/ivacaftor treatment, 46 (39.7%) reported adverse effects related to lumacaftor/ivacaftor, with the vast majority (82.2%) being pulmonary adverse effects, and 20 (17.2%) discontinued lumacaftor/ivacaftor because of adverse effects. The mean change in FEV1% predicted was 0.11% (range: -39% to +20%; P = 0.9). Nineteen individuals had an FEV1% predicted of 40% or less before treatment, and there was a higher percentage of patients in this subgroup who reported adverse effects (57.9%) and a higher percentage of patients who discontinued lumacaftor/ivacaftor (31.6%). Female sex was associated with a higher odds of drug discontinuation (adjusted odds ratio, 3.12, 95% confidence interval, 1.04-9.38).

Conclusions: This study highlights the prevalence of adverse effects in a CF population newly exposed to lumacaftor/ivacaftor and demonstrates a relatively high rate of drug intolerance.

Keywords: CFTR modulators; cystic fibrosis; post-marketing study.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / adverse effects*
  • Aminophenols / therapeutic use*
  • Aminopyridines / adverse effects*
  • Aminopyridines / therapeutic use*
  • Benzodioxoles / adverse effects*
  • Benzodioxoles / therapeutic use*
  • Child
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Drug Combinations
  • Dyspnea / etiology
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Logistic Models
  • Lung / metabolism
  • Male
  • Middle Aged
  • Mutation
  • Quinolones / adverse effects*
  • Quinolones / therapeutic use*
  • Retrospective Studies
  • Young Adult


  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Drug Combinations
  • Quinolones
  • lumacaftor, ivacaftor drug combination
  • Cystic Fibrosis Transmembrane Conductance Regulator