Theratyping cystic fibrosis patients to guide elexacaftor/tezacaftor/ivacaftor out-of-label prescription.
Journal
The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
18
01
2023
accepted:
16
08
2023
medline:
23
10
2023
pubmed:
12
9
2023
entrez:
11
9
2023
Statut:
epublish
Résumé
Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator ( CFTR activity correction was studied by short-circuit current in HNEC cultures at basal state (dimethyl sulfoxide (DMSO)) and after ETI incubation and expressed as percentage of normal (wild-type (WT)) CFTR activity after sequential addition of forskolin and Inh-172 (Δ 11 pwCF carried variants eligible for ETI according to the FDA label and 28 carried variants not listed by the FDA. ETI significantly increased CFTR activity of FDA-approved Primary nasal epithelial cells hold promise for expanding the prescription of CFTR modulators in pwCF carrying rare mutants. Additional variants should be discussed for ETI indication.
Sections du résumé
BACKGROUND
Around 20% of people with cystic fibrosis (pwCF) do not have access to the triple combination elexacaftor/tezacaftor/ivacaftor (ETI) in Europe because they do not carry the F508del allele on the CF transmembrane conductance regulator (
METHODS
CFTR activity correction was studied by short-circuit current in HNEC cultures at basal state (dimethyl sulfoxide (DMSO)) and after ETI incubation and expressed as percentage of normal (wild-type (WT)) CFTR activity after sequential addition of forskolin and Inh-172 (Δ
RESULTS
11 pwCF carried variants eligible for ETI according to the FDA label and 28 carried variants not listed by the FDA. ETI significantly increased CFTR activity of FDA-approved
CONCLUSIONS
Primary nasal epithelial cells hold promise for expanding the prescription of CFTR modulators in pwCF carrying rare mutants. Additional variants should be discussed for ETI indication.
Identifiants
pubmed: 37696564
pii: 13993003.00110-2023
doi: 10.1183/13993003.00110-2023
pii:
doi:
Substances chimiques
elexacaftor
RRN67GMB0V
ivacaftor
1Y740ILL1Z
tezacaftor
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Dimethyl Sulfoxide
YOW8V9698H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.
Déclaration de conflit d'intérêts
Conflict of interest: P.R. Burgel reports grants from Vertex and GSK, outside the submitted work. N. Stremler reports advisory board participation with Vertex, outside the submitted work. B. Douvry reports grants and advisory board participation with Vertex, outside the submitted work. L. Le Clainche reports payment for expert testimony from Zambon, Novartis and Viatris, outside the submitted work. C. Marguet reports consulting fees from Vertex and Mylan, and payment for expert testimony from Vertex and Zambon, outside the submitted work. P. de Carli reports grants from Vaincre la Mucoviscidose, outside the submitted work. I. Sermet-Gaudelus reports support for the present manuscript from Vaincre la Mucoviscidose and Mucoviscidose ABCF2. I. Sermet-Gaudelus also reports, outside the submitted work, grants from Agence Nationale pour la Recherche, Assistance Publique–Hôpitaux de Paris and Vertex Innovation Award, and consulting fees and travel support from Vertex therapeutics. All other authors have nothing to disclose.