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Cited by 98Cystic Fibrosis Research AdvancesInhalation and Respiratory Drug DeliveryChronic Obstructive Pulmonary Disease (COPD) Research

A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis

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Habib, Al-Rahim R., Kajbafzadeh, Majid, Desai, Sameer, Yang, Connie L., Skolnik, Kate, Quon, Bradley S.·2019·Scientific Reports
DOI 10.1038/s41598-019-43652-2PMC PMC6510767
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Abstract

Several placebo-controlled trials have been recently published evaluating novel therapies targeting the defective CFTR protein. This systematic review examines the clinical efficacy and safety of CFTR modulators in individuals with cystic fibrosis (CF) with specific genetic mutations. Online sources were searched for placebo-controlled, parallel-design clinical trials investigating CFTR modulators from January 1, 2005 to March 31, 2018. The primary outcome of interest was FEV 1 % predicted (ppFEV 1 ). Fourteen RCTs met our eligibility criteria. The largest improvement in ppFEV 1 favouring treatment was observed for ivacaftor (IVA) in G551D individuals (≥6 years old). Both tezacaftor-ivacaftor (TEZ-IVA) and lumacaftor-ivacaftor (LUM-IVA) also improved ppFEV 1 in F508del homozygous individuals but there was increased reporting of respiratory adverse events with LUM-IVA compared to placebo. IVA also significantly improved ppFEV 1 in a sub-group of individuals ≥18 years old with an R117H mutation. No significant improvements in ppFEV 1 were observed for IVA, LUM, or TEZ in F508del homozygous individuals, LUM or LUM-IVA in F508del heterozygous individuals, or ataluren in individuals with a nonsense mutation. Significant improvements in ppFEV 1 and other clinical outcomes were observed for IVA in G551D individuals, TEV-IVA and LUM-IVA in F508del homozygous individuals, and IVA in adults with a R117H mutation.

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  • Ivacaftor and tezacaftor-ivacaftor are approved therapies with well-characterized safety profiles.

    “Ivacaftor and tezacaftor–ivacaftor, two components of this triple combination, are approved therapies, with well-characterized safety profiles.10-12,30”

    From Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele (2019) · cites this paper as [30]

    The Discussion (page not provided) concludes that ivacaftor is safe for people with a G551D mutation and that tezacaftor–ivacaftor is safer than lumacaftor–ivacaftor in F508del-homozygous individuals. It also says long-term placebo-controlled effects remain unclear. Our copy supports safety findings in those studied groups, but does not establish that both therapies are approved or that their safety profiles are well characterized without those limits. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Habib, A.-R. R., Kajbafzadeh, M., Desai, S., Yang, C. L., Skolnik, K., & Quon, B. S.
Affiliations
  • The University of Sydney (AU)
  • University of British Columbia (CA)
  • University of Calgary (CA)
Corresponding author
Quon, Bradley S.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-05-10
Volume
9
Issue
1
Pages
7234-7234
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-43652-2
PMC
PMC6510767
OpenAlex
W2944465347
Cited by
98
References
2
Citations by year
2026: 7 · 2025: 9 · 2024: 7 · 2023: 18 · 2022: 12 · 2021: 11 · 2020: 23 · 2019: 11
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Michael Smith Health Research BC
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
Keywords
cystic fibrosis, CFTR modulators, ivacaftor, tezacaftor/ivacaftor, lumacaftor/ivacaftor, ataluren, F508del mutation, G551D mutation, R117H mutation, FEV1, respiratory adverse events, clinical efficacy, drug safety, nonsense mutation
MeSH terms
Aminophenols, Cystic Fibrosis, Forced Expiratory Volume, Humans, Indoles, Quinolones, Treatment Outcome, Gene Deletion, Cystic Fibrosis Transmembrane Conductance Regulator, Polymorphism, Single Nucleotide, Benzodioxoles, Chloride Channel Agonists

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