Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People With Cystic Fibrosis and Preexisting Advanced Lung Disease at Treatment Initiation

Abstract

Background

Elexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased FEV₁, decreased exacerbation frequency, and BMI in people with cystic fibrosis. Landmark clinical trials excluded patients with advanced lung disease as defined by FEV₁ < 40%. We have previously reported an improvement in % predicted FEV₁ of 7.9% after 3 months of ETI in people with advanced cystic fibrosis lung disease (ACFLD). The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI after 24 months of treatment in people with ACFLD.

Research Question

What are the long-term effects of ETI on people with cystic fibrosis and pre-existing advanced lung disease on lung function, BMI, and pulmonary exacerbation rates?

Study Design and Methods

We conducted a retrospective cohort study of adult patients with FEV₁ < 40% and/or other high-risk features defined by the 2019 Cystic Fibrosis Foundation lung transplant guidelines who were started on ETI between September 2019 and February 2020. Response to therapy was assessed with repeat spirometry measured at 12 and 24 months. All measurements were taken outside of an acute exacerbation. Demographics and clinical data including BMI and pulmonary exacerbation frequency were extracted from the medical record.

Results

A total of 57 of 64 people with ACFLD showed improved lung function with a mean change in % predicted FEV₁ of 6.74% (P ≤ .001; 95% CI, 4.25%-9.23%) between baseline and 24 months of treatment. BMI increased by a mean change of 1.55 kg/m² (P ≤ .001; 95% CI, 0.93-2.18 kg/m²) during this interval. The annual exacerbation rate between the year before ETI and 24 months on ETI declined with a median of 1 less per year (P = .0007).

Interpretation

People with ACFLD experienced a significant increase in lung function at 24 months on ETI, but less than those with higher baseline lung function compared with prior studies. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.