Frequency of CFTR variants in southern Brazil and indication for modulators therapy in patients with cystic fibrosis

Abstract

This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta^®), 44.6 % for the use of Tezacaftor/Ivacaftor (Symdeko^®), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi^®). For the use of Ivacaftor (Kalydeco^®), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

Keywords:
Cystic fibrosis; CFTR; causing variant; personalized medicine