Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis A Clinical Trial

the PROMISE Study Group

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. Objectives: PROMISE is a postapproval study to understand the broad effects of ETI through 30 months’ clinical use in a more diverse U.S. patient population with planned analyses after 6 months. Methods: Prospective, observational study in 487 people with CF age 12 years or older with at least one F508del allele starting ETI for the first time. Assessments occurred before and 1, 3, and 6 months into ETI therapy. Outcomes included change in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI), and self-reported respiratory symptoms. Measurements and Main Results: Average age was 25.1 years, and 44.1% entered the study using tezacaftor/ivacaftor or lumacaftor/ivacaftor, whereas 6.7% were using ivacaftor, consistent with F508del homozygosity and G551D allele, respectively. At 6 months into ETI therapy, ppFEV1 improved 9.76 percentage points (95% confidence interval [CI], 8.76 to 10.76) from baseline, cystic fibrosis questionnaire–revised respiratory domain score improved 20.4 points (95% CI, 18.3 to 22.5), and sweat chloride decreased 241.7 mmol/L (95% CI, 243.8 to 239.6). BMI also significantly increased. Changes were larger in those naive to modulators but substantial in all groups, including those treated with ivacaftor at baseline. Conclusions: ETI by clinical prescription provided large improvements in lung function, respiratory symptoms, and BMI in a diverse population naive to modulator drug therapy, using existing two-drug combinations, or using ivacaftor alone. Each group also experienced significant reductions in sweat chloride concentration, which correlated with improved ppFEV1 in the overall study population.

Original languageEnglish (US)
Pages (from-to)529-539
Number of pages11
JournalAmerican journal of respiratory and critical care medicine
Volume205
Issue number5
DOIs
StatePublished - Mar 1 2022

Bibliographical note

Funding Information:
Supported by the Cystic Fibrosis Foundation. Additional programmatic funding that supported this research was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072482 [S.M.R. and G.M.S.]) and NHLBI (P30DK089507 [D.P.N.], R35HL135816 [S.M.R.], UL1TR003096 [S.M.R.], UL1 TR002535 [S.D.S.], K24HL14166 [L.R.H.], and K08HL138153 [G.M.S.]). Funding agencies had no role in the design, management, data collection, analyses, or interpretation of the data or in the writing of the manuscript or the decision to submit for publication. The views expressed in this publication are those of the authors and not necessarily those of the Cystic Fibrosis Foundation or NIH.

Publisher Copyright:
Copyright © 2022 by the American Thoracic Society.

Keywords

  • Clinical trial
  • Cystic fibrosis
  • Elexacaftor/tezacaftor/ivacaftor
  • Modulators
  • PROMISE

PubMed: MeSH publication types

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

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