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Use of elexacaftor/tezacaftor/ivacaftor among cystic fibrosis lung transplant recipients

  • Kathleen J. Ramos
    Correspondence
    Corresponding author.
    Affiliations
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, 1959 NE Pacific Street, Box 356522, Seattle, WA 98195, USA
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  • Jennifer S. Guimbellot
    Affiliations
    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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  • Maryam Valapour
    Affiliations
    Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA
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  • Lauren E. Bartlett
    Affiliations
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, 1959 NE Pacific Street, Box 356522, Seattle, WA 98195, USA
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  • Travis Hee Wai
    Affiliations
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, 1959 NE Pacific Street, Box 356522, Seattle, WA 98195, USA
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  • Christopher H. Goss
    Affiliations
    Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, 1959 NE Pacific Street, Box 356522, Seattle, WA 98195, USA

    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington, Seattle, WA, USA
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  • Joseph M. Pilewski
    Affiliations
    Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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  • Albert Faro
    Affiliations
    Cystic Fibrosis Foundation, Bethesda, MD, USA
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  • Joshua M. Diamond
    Affiliations
    Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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  • for theCFLTC Study Group
    Author Footnotes
    1 CFLTC Study Group:Selim Arcasoy, Columbia University Irving Medical CenterLauren E. Bartlett, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonLuke Benvenuto, Columbia University Irving Medical CenterJason D. Christie, Department of Medicine, University of PennsylvaniaEmily Clausen, Department of Medicine, University of PennsylvaniaElliott Dasenbrook, Cleveland ClinicJoshua M. Diamond, Department of Medicine, University of PennsylvaniaDaniel F. Dilling, Loyola University ChicagoLerin J. Eason, Duke UniversityAlbert Faro, Cystic Fibrosis FoundationChristopher H. Goss, Departments of Medicine and Pediatrics, University of WashingtonRamsey Hachem, Washington University in St. LouisSteven R. Hays, Department of Medicine, University of California, San FranciscoMarshall I. Hertz, University of MinnesotaShahrzad Lari, University of California Los AngelesErika D. Lease, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonErin Lowery, University of WisconsinChristian Merlo, Johns Hopkins UniversityEric D. Morrell, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonMatthew Morrell, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of PittsburghIsabel P. Neuringer, Massachusetts General Hospital, Boston, Mass.Shreena Patel, Columbia University Irving Medical CenterJagadish R Patil, University of MinnesotaJoseph M. Pilewski, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of PittsburghKathleen J. Ramos, University of WashingtonJulie Safirstein, Department of Medicine, University of PennsylvaniaDavid M. Sayah, University of California, San FranciscoPali Shah, Johns Hopkins UniversityJonathan P Singer, Department of Medicine, University of California, San FranciscoLianne G. Singer, University Health Network, University of TorontoLaurie D Snyder, Duke UniversityStuart C. Sweet, Professor of Pediatrics, Washington University in St. LouisJason Turowski, Cleveland ClinicMaryam Valapour, Cleveland ClinicS. Sam Weigt, University of California Los Angeles
  • Author Footnotes
    1 CFLTC Study Group:Selim Arcasoy, Columbia University Irving Medical CenterLauren E. Bartlett, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonLuke Benvenuto, Columbia University Irving Medical CenterJason D. Christie, Department of Medicine, University of PennsylvaniaEmily Clausen, Department of Medicine, University of PennsylvaniaElliott Dasenbrook, Cleveland ClinicJoshua M. Diamond, Department of Medicine, University of PennsylvaniaDaniel F. Dilling, Loyola University ChicagoLerin J. Eason, Duke UniversityAlbert Faro, Cystic Fibrosis FoundationChristopher H. Goss, Departments of Medicine and Pediatrics, University of WashingtonRamsey Hachem, Washington University in St. LouisSteven R. Hays, Department of Medicine, University of California, San FranciscoMarshall I. Hertz, University of MinnesotaShahrzad Lari, University of California Los AngelesErika D. Lease, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonErin Lowery, University of WisconsinChristian Merlo, Johns Hopkins UniversityEric D. Morrell, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of WashingtonMatthew Morrell, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of PittsburghIsabel P. Neuringer, Massachusetts General Hospital, Boston, Mass.Shreena Patel, Columbia University Irving Medical CenterJagadish R Patil, University of MinnesotaJoseph M. Pilewski, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of PittsburghKathleen J. Ramos, University of WashingtonJulie Safirstein, Department of Medicine, University of PennsylvaniaDavid M. Sayah, University of California, San FranciscoPali Shah, Johns Hopkins UniversityJonathan P Singer, Department of Medicine, University of California, San FranciscoLianne G. Singer, University Health Network, University of TorontoLaurie D Snyder, Duke UniversityStuart C. Sweet, Professor of Pediatrics, Washington University in St. LouisJason Turowski, Cleveland ClinicMaryam Valapour, Cleveland ClinicS. Sam Weigt, University of California Los Angeles
Published:April 23, 2022DOI:https://doi.org/10.1016/j.jcf.2022.04.009

      Highlights

      • A small proportion (13%) of CF lung transplant recipients have been prescribed ETI.
      • Most recipients were prescribed ETI for sinus disease or GI symptoms.
      • Many (30–40%) CF lung transplant recipients stopped ETI due to side effects.
      • Hemoglobin and hemoglobin A1c may improve with ETI use after transplant.

      Abstract

      Background

      Cystic fibrosis (CF) lung transplant (LT) recipients may warrant treatment with elexacaftor/tezacaftor/ivacaftor (ETI) to improve extrapulmonary manifestations of CF. Our objectives were to identify reasons for prescribing ETI after LT and evaluate changes in body mass index (BMI), hemoglobin A1c, hemoglobin, and liver enzymes.

      Methods

      This was an electronic health record-based cohort study, October 2019-September 2020, at 14 CF LT Consortium sites in North America. The study included CF LT recipients prescribed ETI after transplant. Differences in BMI, A1c, and hemoglobin were assessed with paired t-tests.

      Results

      There were 94 patients prescribed ETI; indications included sinus disease (68%), GI symptoms (39%), or low BMI (19%). Prescriptions were written by CF physicians (34%), LT physicians (27%), or physicians who practice both CF and LT (39%). Forty patients (42%) stopped ETI at a median of 56 days [IQR 26, 139] after start/prescription date. ETI was not associated with a significant change in BMI (0.2 kg/m2, 95% CI [-0.1, 0.6], p = 0.150), but was associated with decreased A1c (0.4%, 95% CI 0.2, 0.7, p = 0.003), and increased hemoglobin for patients with anemia (0.6 g/dL, 95% CI 0.2, 1.0, p = 0.007). Three people (3%) stopped ETI due to elevated transaminases.

      Conclusions

      ETI is rarely prescribed for non-pulmonary indications after LT for CF. Further study is needed to determine the risks and benefits of ETI in the CF lung transplant population given the potential for drug interactions, side effects leading to discontinuation of ETI, and the possible mechanisms for ETI to positively impact long-term post-transplant outcomes.

      Keywords

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