Global prevalence of CFTR variants with respect to their responsiveness to elexacaftor-tezacaftor-ivacaftor

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10504252" target="_blank" >RIV/00064203:_____/25:10504252 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10504252

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4.fecM23xs" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=4.fecM23xs</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jcf.2025.10.007" target="_blank" >10.1016/j.jcf.2025.10.007</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Global prevalence of CFTR variants with respect to their responsiveness to elexacaftor-tezacaftor-ivacaftor

Popis výsledku v původním jazyce

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor (ETI) is mostly approved in people with cystic fibrosis (pwCF) with a p.Phe508del CFTR variant. The US Food and Drug Administration (FDA) approved ETI for an additional 177 rare CFTR variants and studies identified 7 non-FDA approved variants also responsive to ETI. The global impact of expanding the ETI label to rare responsive CFTR variants on the number of eligible pwCF is unknown. METHODS: Data were obtained from CF registries and individual CF clinics in countries without registries. Individuals were classified according to five mutually-exclusive categories (1) at least one p.Phe508del variant (2) at least one of the 177 FDA-approved variants (3) at least one non-FDA-approved variant responsive to ETI (4) two variants resulting in no CFTR protein (5) all other variants. The first 3 groups were considered responsive to ETI, group 4 was nonresponsive and group 5 of undetermined responsiveness. RESULTS: Data were obtained from 95,838 pwCF living in 69 countries: 78,566 (82.0 %) had at least one p.Phe508del, 6175 (6.4 %) at least one FDA-approved variants, and 2981 (3.1 %) at least one non-FDA-approved responsive variants. Two variants resulting in no CFTR protein were found in 3574 (3.7 %) and other variant combinations in 4490 (4.7 %). The prevalence of p.Phe508del ranged from 7 % to 98 % in individual countries and expanding the eligibility to responsive non-p.Phe508del variants resulted in greatest eligibility increase in countries with low p.Phe508del prevalence. CONCLUSION: Expanding the label of ETI to rare responsive CFTR variants will make at least 91.5 % of pwCF eligible to this disease-modifying therapy.

Název v anglickém jazyce

Global prevalence of CFTR variants with respect to their responsiveness to elexacaftor-tezacaftor-ivacaftor

Popis výsledku anglicky

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor (ETI) is mostly approved in people with cystic fibrosis (pwCF) with a p.Phe508del CFTR variant. The US Food and Drug Administration (FDA) approved ETI for an additional 177 rare CFTR variants and studies identified 7 non-FDA approved variants also responsive to ETI. The global impact of expanding the ETI label to rare responsive CFTR variants on the number of eligible pwCF is unknown. METHODS: Data were obtained from CF registries and individual CF clinics in countries without registries. Individuals were classified according to five mutually-exclusive categories (1) at least one p.Phe508del variant (2) at least one of the 177 FDA-approved variants (3) at least one non-FDA-approved variant responsive to ETI (4) two variants resulting in no CFTR protein (5) all other variants. The first 3 groups were considered responsive to ETI, group 4 was nonresponsive and group 5 of undetermined responsiveness. RESULTS: Data were obtained from 95,838 pwCF living in 69 countries: 78,566 (82.0 %) had at least one p.Phe508del, 6175 (6.4 %) at least one FDA-approved variants, and 2981 (3.1 %) at least one non-FDA-approved responsive variants. Two variants resulting in no CFTR protein were found in 3574 (3.7 %) and other variant combinations in 4490 (4.7 %). The prevalence of p.Phe508del ranged from 7 % to 98 % in individual countries and expanding the eligibility to responsive non-p.Phe508del variants resulted in greatest eligibility increase in countries with low p.Phe508del prevalence. CONCLUSION: Expanding the label of ETI to rare responsive CFTR variants will make at least 91.5 % of pwCF eligible to this disease-modifying therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Journal of Cystic Fibrosis

ISSN

1569-1993

e-ISSN

1873-5010

Svazek periodika

24

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

10

Strana od-do

1017-1026

Kód UT WoS článku

001633073200002

EID výsledku v databázi Scopus

2-s2.0-105023412096