Long-Term Clinical Efficacy of Elexacaftor-Tezacaftor-Ivacaftor in People with Cystic Fibrosis & Pre-existing Advanced Lung Disease at Treatment Initiation.

Abstract

BackgroundElexacaftor-tezacaftor-ivacaftor (ETI) is associated with increased forced expiratory volume in the first second (FEV1), decreased exacerbation frequency, and increased body mass index (BMI) in people with Cystic Fibrosis (pwCF) [1, 2]. Landmark clinical trials excluded patients with advanced lung disease (ALD) as defined by FEV1<40%. We have previously reported an improvement in ppFEV1 of 7.9% after 3 months of ETI in people with CF and ALD (ACFLD)[3]. The long-term effects of ETI on this cohort are unknown. This study reports the efficacy of ETI following 24 months of treatment in people with ACFLD. Study DesignWe conducted a retrospective cohort study of adult patients with FEV1<40% and/or other high-risk features defined by the 2019 CFF 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. Results57 of 64 people with ACFLD showed improved lung function with a mean change in ppFEV1 of 6.74% (p = <0.001, 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 = <0.001, 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 fewer per year (p = 0.0007). InterpretationPeople with ACFLD experienced a significant increase in lung function at 24 months on ETI, although less than those with higher baseline lung function compared to prior studies [1, 2]. They also had an increase in BMI and a decline in the rate of annual pulmonary exacerbations.