Cited by 140Cystic Fibrosis Research AdvancesPharmacogenetics and Drug MetabolismInhalation and Respiratory Drug Delivery

Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study

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Bower, Julie K., Volkova, Nataliya, Ahluwalia, Neil, Sahota, Gurvaneet, Xuan, Fengjuan, Chin, Anna, Weinstock, Tanya G., Ostrenga, Josh +1 more·2023·Journal of Cystic Fibrosis

Abstract

Background Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele. To assess long-term effects of ELX/TEZ/IVA under real-world conditions of use, a 5-year observational registry-based study is being conducted. We report interim results from the first 2 years of follow-up. Methods The study included people with CF in the US Cystic Fibrosis Foundation Patient Registry (CFFPR) who initiated ELX/TEZ/IVA between October 2019 and December 2020. Pulmonary exacerbations (PEx), percent predicted forced expiratory volume in 1 second (ppFEV 1 ), hospitalizations, bacterial pathogens, body mass index (BMI), CF complications and comorbidities, and liver function tests (LFTs) after treatment initiation were compared with the 5-year pre-treatment period. Death and lung transplantation were assessed relative to 2019 CFFPR data. Results 16,116 people with CF were included (mean treatment duration 20.4 months). Among those with 5 years of pre-treatment data, mean PEx/patient/year declined to 0.18 (95% CI: 0.17, 0.19) in Years 1 and 2 post-treatment from 0.86 (95% CI: 0.83, 0.88) in the baseline year (79% reduction), after a continued increase observed pre-treatment. Similarly, a decline in mean hospitalizations/patient/year was observed in Year 1 that was sustained in Year 2 (74% reduction from baseline year). The mean absolute change in ppFEV 1 from baseline was +8.2 percentage points (95% CI: 8.0, 8.4) in Year 1 and +8.9 percentage points (95% CI: 8.7, 9.1) in Year 2, after a continued decline observed pre-treatment. Positive bacterial cultures decreased for all evaluated pathogens, and mean BMI increased by 1.6 kg/m 2 (95% CI: 1.5, 1.6) by Year 2. No new safety concerns were identified based on evaluation of CF complications, comorbidities, and LFTs. The annualized rates of death (0.47% [95% CI: 0.39, 0.55]) and lung transplantation (0.16% [95% CI: 0.12, 0.22]) were considerably lower than reported in 2019 (1.65% and 1.08%, respectively). Conclusions ELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and lower prevalence of positive bacterial cultures. Additionally, there was a 72% lower rate of death and 85% lower rate of lung transplantation relative to the year before ELX/TEZ/IVA availability. These results, from the largest cohort of ELX/TEZ/IVA-treated people to date, extend our understanding of the broad clinical benefits of ELX/TEZ/IVA.

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Crossref · 10.1016/j.jcf.2023.03.002

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Authors
Bower, J. K., Volkova, N., Ahluwalia, N., Sahota, G., Xuan, F., Chin, A., Weinstock, T. G., Ostrenga, J., & Elbert, A.
Affiliations
  • Vertex Pharmaceuticals (United States) (US)
  • Cystic Fibrosis Foundation (US)
Corresponding author
Bower, Julie K.
Venue
Journal of Cystic Fibrosis
Publisher
Elsevier BV
Published
2023-07
Volume
22
Issue
4
Pages
730-737
ISSN
1569-1993 (ISSN-L)
OpenAlex
W4353046996
Cited by
140
References
22
Citations by year
2026: 35 · 2025: 51 · 2024: 33 · 2023: 21
FWCI
25.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Cystic Fibrosis (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Vertex Pharmaceuticals Incorporated
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
Keywords
elexacaftor/tezacaftor/ivacaftor, CFTR modulator therapy, F508del-CFTR, pulmonary exacerbations, hospitalization reduction, FEV1 decline, pathogenic bacteria, body mass index, liver function tests, lung transplantation, long-term safety, real-world effectiveness
MeSH terms
Aminophenols, Cystic Fibrosis, Humans, Indoles, Mutation, Pyrazoles, Pyridines, Pyrrolidines, Registries, Quinolones, Cystic Fibrosis Transmembrane Conductance Regulator, Benzodioxoles, Chloride Channel Agonists

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