Comparison of the Effect of CFTR Modulators elexacaftor/tezacaftor/ivacaftor and lumacaftor/ivacaftor via Serum Human Epididymis Protein 4 Concentration in p.Phe508del-CFTR Homozygous Cystic Fibrosis Patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10503273" target="_blank" >RIV/00064203:_____/25:10503273 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/25:10503273

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=5OCu8qy64L" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=5OCu8qy64L</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/jcm14176188" target="_blank" >10.3390/jcm14176188</a>

Result language

angličtina

Original language name

Comparison of the Effect of CFTR Modulators elexacaftor/tezacaftor/ivacaftor and lumacaftor/ivacaftor via Serum Human Epididymis Protein 4 Concentration in p.Phe508del-CFTR Homozygous Cystic Fibrosis Patients

Original language description

Elevated human epididymis protein 4 (HE4) levels decreased in patients with CF (pwCF) in response to CFTR-specific drugs and negatively correlated with FEV1% predicted values (ppFEV1). Objectives: Although elexacaftor/tezacaftor/ivacaftor (ETI, Kaftrio(®)) demonstrates more substantial effectiveness than lumacaftor/ivacaftor (LUM/IVA, Orkambi(®)) in pwCF, plasma biomarkers have not been used to compare treatment efficacy. Hence, our aim was to correlate the change in HE4 levels and the clinical effects of these CFTR modulators (CFTRm). Methods: Serum HE4 concentrations were measured in a total of 123 pwCF homozygous for the p.Phe508del-CFTR variant before treatment and 1-6 months after either ETI or LUM/IVA administration. A correlation between serum HE4 and ppFEV1 was assessed using the Spearman test. HE4 protein levels were also analyzed in the supernatants of p.Phe508del-CFTR CFBE 41o- cells before and after treatment with these CFTRm, and their direct effect on CFTR function was monitored by the whole-cell patch-clamp technique. Results: Serum HE4 levels were reduced below baseline after 3 months of either ETI or LUM/IVA (mean delta HE4: -38.5 vs. -18.5 pmol/L, respectively) when the mean change of ppFEV1 was 13.6 vs. 1.6% and remained decreased up to 6 months. A significant inverse correlation between HE4 and ppFEV1 was observed in both study cohorts (r = -0.537 and r = -0.575, respectively; p &lt; 0.0001). In agreement with ex vivo results, the effect on p.Phe508del-CFTR was more pronounced by ETI than LUM/IVA in CFBE cells, showing a larger improvement in p.Phe508del-CFTR function and reductions in HE4 levels at 24 h. Conclusions: Serum HE4 negatively correlates with lung function improvement and monitors better drug efficacy in pwCF under ETI than LUM/IVA.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30203 - Respiratory systems

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Clinical Medicine

ISSN

2077-0383

e-ISSN

2077-0383

Volume of the periodical

14

Issue of the periodical within the volume

17

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

6188

UT code for WoS article

001571366900001

EID of the result in the Scopus database

2-s2.0-105016268170