Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR A Clinical Trial

on behalf of the PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Rationale: The combination of lumacaftor (LUM) and ivacaftor (IVA) is an approved CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator treatment for homozygous F508del patients with CF. Objectives: To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting. Methods: This longitudinal cohort study, performed at 38 centers in the U.S. CF Therapeutics Development Network, enrolled homozygous F508del patients with CF ages 6 years old and older with no prior exposure to LUM/IVA. Study assessments were performed at baseline and at 1, 3, 6, and 12 months after LUM/IVA initiation. Results: A total of 193 patients initiated LUM/IVA, and 85% completed the study through 1 year. Baseline mean percent-predicted forced expiratory volume in 1 second (ppFEV 1) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV 1 was observed from baseline to any of the follow-up time points, with a mean absolute change at 12 months of -0.3 (95% confidence interval [CI], -1.8 to 1.2). Body mass index improved from baseline to 12 months (mean change, 0.8 kg/m 2; P  < 0.001). Sweat chloride decreased from baseline to 1 month (mean change, -18.5 mmol/L; 95% CI, -20.7 to -16.3; P  < 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment. Conclusions: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection.Clinical trial registered with (NCT02477319).

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalAnnals of the American Thoracic Society
Issue number1
StatePublished - Jan 2021

Bibliographical note

Funding Information:
Supported by Cystic Fibrosis Foundation Therapeutics (SAGEL14K1, HAMBLE14K1, and ROWE19R0) and the U.S. National Institutes of Health (UL1 TR002535, DK089507, P30DK072482, and R35HL135816).

Publisher Copyright:
Copyright © 2021 by the American Thoracic Society


  • Clinical effectiveness
  • Cystic fibrosis
  • Ivacaftor
  • Lumacaftor
  • Postapproval study
  • Aminopyridines
  • Humans
  • Male
  • Aminophenols
  • Quinolones
  • Forced Expiratory Volume
  • Young Adult
  • Benzodioxoles
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Cystic Fibrosis/drug therapy
  • Adolescent
  • Adult
  • Female
  • Mutation
  • Child
  • Longitudinal Studies
  • Cohort Studies

PubMed: MeSH publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Multicenter Study
  • Journal Article
  • Research Support, N.I.H., Extramural


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