ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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A One-Year Retrospective Analysis of the Effect of Elexacaftor-Tezacaftor-Ivacaftor on Lung Function in Cystic Fibrosis Patients with Advanced Lung Disease
Session Title
TP32 - TP032 EPIDEMIOLOGY, BIOMARKERS, AND THERAPY IN CF AND NON-CF BRONCHIECTASIS
Abstract
A2026 - A One-Year Retrospective Analysis of the Effect of Elexacaftor-Tezacaftor-Ivacaftor on Lung Function in Cystic Fibrosis Patients with Advanced Lung Disease
Author Block: B. Bermingham1, A. Rueschhoff2, G. Ratti2, A. Nesmith3, P. A. Flume1, G. M. Solomon3, L. Cohen2, B. Garcia1; 1Pulmonary, Critical Care, Allergy & Sleep Medicine, Medical University of South Carolina, Charleston, SC, United States, 2Pulmonary and Critical Care, UT Southwestern, Dallas, TX, United States, 3Dept of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Rationale: The CFTR modulators elexacaftor-tezacaftor-ivacaftor form a triple combination (TC) therapy shown to improve clinical outcomes in cystic fibrosis (CF) patients. While patients with advanced lung disease (ALD) were excluded from prior phase III trials, our research group has previously shown short-term clinical improvement in lung function. These improvements altered patients’ guideline-based indications regarding lung transplant discussion or referral, with fewer indications for lung transplant referral following initiation of TC therapy. The objective of this study was to provide efficacy and safety data following 1 year of TC therapy in genetically eligible patients who have pre-existing ALD.
Methods: We conducted a multi-center retrospective cohort study of adult patients with FEV1<40% and/or other high-risk features as defined by the 2019 CFF lung transplant guidelines started on TC therapy between November 2019 and February 2020. Response to therapy was assessed with repeat measurement of forced expiratory volume in 1 second percent predicted (FEV1pp), forced vital capacity percent predicted (FVCpp), and body mass index (BMI) measured at initial follow up between 2-12 weeks and at 1 year following the initiation of therapy. Drug-related adverse events, drug toxicity monitoring, and exacerbation frequency were obtained from the medical record.
Results: A total of 50 patients were identified and started on TC between November 2019 and February 2020. Mean age was 31.5 years and 53% of patients were homozygous for the F508del CFTR mutation. High-risk features as defined by the 2019 CF lung transplant guidelines were identified in 42% of cases. Mean FEV1pp increased 7.9% ± 5.0 (P<0.05) at initial follow up. Of the patients with 1 year follow up data FEV1pp remained increased 7.4% ±7.0 (P<0.05) over baseline and FVCpp improved by 7.5% ±8.12 (P<0.05). BMI increased by a mean of 1.93 kg/m2 ± 2.56 (P<0.05) over the course of 1 year. There was one death among the cohort during the observation period, and no drug-related adverse events requiring treatment discontinuation. Additional data from partner sites is pending and will be available by February 2021.
Conclusions: Patients with ALD started on TC therapy demonstrated improvements in FEV1pp, FVCpp, and BMI that were sustained over the initial 12 months of therapy. Adverse events requiring prolonged treatment discontinuation of therapy were not observed. Further registry studies are needed to elucidate how this improvement in lung function alters disease trajectory and lung transplantation timing.
Author Block: B. Bermingham1, A. Rueschhoff2, G. Ratti2, A. Nesmith3, P. A. Flume1, G. M. Solomon3, L. Cohen2, B. Garcia1; 1Pulmonary, Critical Care, Allergy & Sleep Medicine, Medical University of South Carolina, Charleston, SC, United States, 2Pulmonary and Critical Care, UT Southwestern, Dallas, TX, United States, 3Dept of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Rationale: The CFTR modulators elexacaftor-tezacaftor-ivacaftor form a triple combination (TC) therapy shown to improve clinical outcomes in cystic fibrosis (CF) patients. While patients with advanced lung disease (ALD) were excluded from prior phase III trials, our research group has previously shown short-term clinical improvement in lung function. These improvements altered patients’ guideline-based indications regarding lung transplant discussion or referral, with fewer indications for lung transplant referral following initiation of TC therapy. The objective of this study was to provide efficacy and safety data following 1 year of TC therapy in genetically eligible patients who have pre-existing ALD.
Methods: We conducted a multi-center retrospective cohort study of adult patients with FEV1<40% and/or other high-risk features as defined by the 2019 CFF lung transplant guidelines started on TC therapy between November 2019 and February 2020. Response to therapy was assessed with repeat measurement of forced expiratory volume in 1 second percent predicted (FEV1pp), forced vital capacity percent predicted (FVCpp), and body mass index (BMI) measured at initial follow up between 2-12 weeks and at 1 year following the initiation of therapy. Drug-related adverse events, drug toxicity monitoring, and exacerbation frequency were obtained from the medical record.
Results: A total of 50 patients were identified and started on TC between November 2019 and February 2020. Mean age was 31.5 years and 53% of patients were homozygous for the F508del CFTR mutation. High-risk features as defined by the 2019 CF lung transplant guidelines were identified in 42% of cases. Mean FEV1pp increased 7.9% ± 5.0 (P<0.05) at initial follow up. Of the patients with 1 year follow up data FEV1pp remained increased 7.4% ±7.0 (P<0.05) over baseline and FVCpp improved by 7.5% ±8.12 (P<0.05). BMI increased by a mean of 1.93 kg/m2 ± 2.56 (P<0.05) over the course of 1 year. There was one death among the cohort during the observation period, and no drug-related adverse events requiring treatment discontinuation. Additional data from partner sites is pending and will be available by February 2021.
Conclusions: Patients with ALD started on TC therapy demonstrated improvements in FEV1pp, FVCpp, and BMI that were sustained over the initial 12 months of therapy. Adverse events requiring prolonged treatment discontinuation of therapy were not observed. Further registry studies are needed to elucidate how this improvement in lung function alters disease trajectory and lung transplantation timing.
