Clinical Outcomes in Concurrent Cohorts of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA)-Treated versus ELX/TEZ/IVA-Ineligible Individuals with Cystic Fibrosis in the US during COVID-19

The initial US launch of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) coincided with the coronavirus disease 2019 (COVID-19) pandemic, altering healthcare-seeking behaviors and possibly resulting in decreased respiratory infection transmission. We evaluated real-world effectiveness of ELX/TEZ/IVA, accounting for potential impact of COVID-19 by comparing outcomes in people with cystic fibrosis (CF) treated with ELX/TEZ/IVA with ELX/TEZ/IVA-ineligible people with CF. This retrospective, observational study used US CF Foundation Patient Registry data (2017–2021) of people with CF aged ≥ 12 years initiating ELX/TEZ/IVA between Q4 2019 and Q3 2021 and a concurrent comparator cohort ineligible for ELX/TEZ/IVA. Primary outcomes (follow-up through 2021 or death) included change in percent predicted forced expiratory volume in 1 s (ppFEV1) from baseline over follow-up, annualized rate of ppFEV1 decline, rate of pulmonary exacerbations (PEx), time to lung transplantation, and overall survival. ppFEV1 increased in ELX/TEZ/IVA-treated individuals through follow-up but decreased in the comparator cohort (+6.20 versus −3.13 percentage points, respectively; mean difference 9.34, 95% confidence interval [CI] 8.84 to 9.85). The annualized rate of ppFEV1 change was −0.03 (95% CI −0.18 to 0.07) in the ELX/TEZ/IVA-treated cohort and −2.24 (95% CI −2.66 to −1.80) in the comparator cohort (relative reduction in rate of decline of 99%; 95% CI 92–103%). Rates of PEx requiring intravenous antibiotics or hospitalization were 0.17 and 0.77 among ELX/TEZ/IVA-treated and comparator cohorts, respectively (77% reduction, 95% CI 74–81%). Proportion undergoing lung transplant was 0.22% and 2.94% in ELX/TEZ/IVA-treated and comparator cohorts, respectively (90% reduction, 95% CI 29–98%). All-cause mortality was 0.76% and 3.45% in ELX/TEZ/IVA-treated and comparator cohorts, respectively (79% reduction; 95% CI 56–88%). During COVID-19, ELX/TEZ/IVA-ineligible people with CF experienced lung function decline and higher rates of PEx, lung transplant, and death versus the ELX/TEZ/IVA-treated cohort, despite infection prevention measures, suggesting ELX/TEZ/IVA’s benefits remain despite the potential bias from protective effects of the pandemic.