Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Advanced Cystic Fibrosis Lung Disease

Elexacaftor/tezacaftor/ivacaftor as rescue therapy in a patient with the cystic fibrosis genotype F508DEL/G1244E

“…The clinical trials of ETI in pwCF who were F/F or heterozygous for F and MF, RF, or G involved patients with mild-moderate lung disease, 1-3 but improvements have also been obtained in pwCF with advanced lung disease, and these have often obviated the need for lung transplantation. [4][5][6][7][8] Our patient had an F/G genotype and had been previously treated with ivacaftor but, after an initial improvement, experienced rapid disease progression (as has been previously described in ivacaftor-treated adults with G mutations), 9 possibly aggravated by Bcc colonization. 10 During her subsequent hospitalization, she did not improve significantly until ETI was administered, and, as all her other treatments remained unchanged, this suggests it played a role in her recovery.…”

“…The clinical trials of ETI in pwCF who were F / F or heterozygous for F and MF , RF , or G involved patients with mild‐moderate lung disease, 1‐3 but improvements have also been obtained in pwCF with advanced lung disease, and these have often obviated the need for lung transplantation 4‐8 …”

Elexacaftor/Tezacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study

“…A short-term retrospective study performed across three large academic CF centres in the United States (US) showed a mean increase in ppFEV 1 of 7.1 in a group of 32 F/F subjects after a mean treatment of 39 days [16]. Another retrospective observational study from the US over one year of ETI administration in a mixed population (F/MF, F/F, F/G, F/RF) of 22 adult patients with ppFEV 1 < 40, showed a mean improvement of ppFEV 1 5.5 after 1 month and of 7.6 after 12 months [17].…”

Cystic fibrosis year in review 2021

“…Expanding usage of ETI to population not studied in the original clinical trials, use for PwCF and ADL, based primarily on a FEV1pp <40% or referral/evaluation for lung transplantation demonstrated improvements in FEV1pp [30][31][32][33][34] , BMI [31][32][33][34] , CFQ-R 32,34 , and decreases in antibiotic use/exacerbations 32,34 . Where reported, oxygen use was decreased/eliminated 32,34 , with one study demonstrating a decrease in noninvasive ventilation use 31 .…”

“…Where reported, oxygen use was decreased/eliminated 32,34 , with one study demonstrating a decrease in noninvasive ventilation use 31 . Most importantly, transplantation status primarily changed in a positive direction, with decreases in transplant related discussions, referrals, and wait list numbers [30][31][32][33] . Overall, lung transplants decreased by 56.4% in France, attributed to ETI, as the COVID related decrease in non -CF indications only dropped 26.4% 31 .…”