Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study
Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) for people with CF (PwCF) after lung transplantation (LTx) has been restrained due to uncertainties regarding efficacy and drug interactions. Given the persistence of extrapulmonary symptoms post-LTx, this prospective study aims to investigate the b...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133425000059 |
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| author | Johanna P. van Gemert Bart Luijk Merel E. Hellemons Klara A. Visser Carina.M.E. Hansen Renske van der Meer C. Tji Gan Hester van der Vaart Onno W. Akkerman Willie N. Steenhuis Marieke Verkleij Harry G.M. Heijerman Erik A.M. Verschuuren |
| author_facet | Johanna P. van Gemert Bart Luijk Merel E. Hellemons Klara A. Visser Carina.M.E. Hansen Renske van der Meer C. Tji Gan Hester van der Vaart Onno W. Akkerman Willie N. Steenhuis Marieke Verkleij Harry G.M. Heijerman Erik A.M. Verschuuren |
| author_sort | Johanna P. van Gemert |
| collection | DOAJ |
| description | Background: Elexacaftor/Tezacaftor/Ivacaftor (ETI) for people with CF (PwCF) after lung transplantation (LTx) has been restrained due to uncertainties regarding efficacy and drug interactions. Given the persistence of extrapulmonary symptoms post-LTx, this prospective study aims to investigate the benefits and safety of ETI for PwCF post-LTx. Methods: Between Nov 2022-Nov 2023 ETI was offered to PwCF post-LTx with at least one F508del mutation in 3 Dutch LTx centers. PwCF were considered eligible if they had either a BMI ≤ 19 kg/m², chronic rhinosinusitis (CRS), uncontrolled diabetes or gastrointestinal (GI) symptoms. BMI, HbA1c, SNOT-22 score, GI Symptom Tracker, CF Questionnaire-Revised (CFQ-R), FEV1, creatinine, changes in calcineurin inhibitor (CNI) doses and levels were compared between baseline and 3 months follow-up. Results: Fifty-five PwCF post-LTx were included, of whom 5 were excluded because of ETI discontinuation due to side effects, within 3 month follow-up. Three months results showed a decrease in SNOT-22 score (p< 0.001) and GI symptoms (all 4, p< 0.05), an increase in BMI (p= 0.012) and CFQ-R (6 domains, p< 0.05). Median CNI daily dose had to be reduced from 6 to 4 mg (p< 0.001), to maintain stable CNI trough levels. Creatinine increased from 110 (87−141) to 115 (92−125) umol/L (p= 0.002). Conclusion: ETI for PwCF post-LTx shows favorable effects on CRS, GI symptoms, and quality of life, but not on BMI and HbA1c. Due to its high cost, careful consideration and further studies are required. Monitoring renal function and CNI trough levels is recommended. |
| format | Article |
| id | doaj-art-a721b5413b3745faa03da7289b86313e |
| institution | Kabale University |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | JHLT Open |
| spelling | doaj-art-a721b5413b3745faa03da7289b86313e2025-02-09T05:02:03ZengElsevierJHLT Open2950-13342025-02-017100210Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA studyJohanna P. van Gemert0Bart Luijk1Merel E. Hellemons2Klara A. Visser3Carina.M.E. Hansen4Renske van der Meer5C. Tji Gan6Hester van der Vaart7Onno W. Akkerman8Willie N. Steenhuis9Marieke Verkleij10Harry G.M. Heijerman11Erik A.M. Verschuuren12Department of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Reprint requests: J.P. van Gemert, Department of Respiratory Diseases, Tuberculosis and Lung transplantation, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the NetherlandsDepartment of Respiratory Diseases, Erasmus MC Transplant Institute, Erasmus University, University Medical Center, Rotterdam, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Pulmonology, Haga Teaching Hospital, The Hague, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsAmsterdam UMC location University of Amsterdam, Emma Children’s Hospital, Child and Adolescent Psychiatry & Psychosocial Care, Amsterdam, the NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the NetherlandsDepartment of Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, Groningen, the NetherlandsBackground: Elexacaftor/Tezacaftor/Ivacaftor (ETI) for people with CF (PwCF) after lung transplantation (LTx) has been restrained due to uncertainties regarding efficacy and drug interactions. Given the persistence of extrapulmonary symptoms post-LTx, this prospective study aims to investigate the benefits and safety of ETI for PwCF post-LTx. Methods: Between Nov 2022-Nov 2023 ETI was offered to PwCF post-LTx with at least one F508del mutation in 3 Dutch LTx centers. PwCF were considered eligible if they had either a BMI ≤ 19 kg/m², chronic rhinosinusitis (CRS), uncontrolled diabetes or gastrointestinal (GI) symptoms. BMI, HbA1c, SNOT-22 score, GI Symptom Tracker, CF Questionnaire-Revised (CFQ-R), FEV1, creatinine, changes in calcineurin inhibitor (CNI) doses and levels were compared between baseline and 3 months follow-up. Results: Fifty-five PwCF post-LTx were included, of whom 5 were excluded because of ETI discontinuation due to side effects, within 3 month follow-up. Three months results showed a decrease in SNOT-22 score (p< 0.001) and GI symptoms (all 4, p< 0.05), an increase in BMI (p= 0.012) and CFQ-R (6 domains, p< 0.05). Median CNI daily dose had to be reduced from 6 to 4 mg (p< 0.001), to maintain stable CNI trough levels. Creatinine increased from 110 (87−141) to 115 (92−125) umol/L (p= 0.002). Conclusion: ETI for PwCF post-LTx shows favorable effects on CRS, GI symptoms, and quality of life, but not on BMI and HbA1c. Due to its high cost, careful consideration and further studies are required. Monitoring renal function and CNI trough levels is recommended.http://www.sciencedirect.com/science/article/pii/S2950133425000059CFLung transplantETI |
| spellingShingle | Johanna P. van Gemert Bart Luijk Merel E. Hellemons Klara A. Visser Carina.M.E. Hansen Renske van der Meer C. Tji Gan Hester van der Vaart Onno W. Akkerman Willie N. Steenhuis Marieke Verkleij Harry G.M. Heijerman Erik A.M. Verschuuren Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study JHLT Open CF Lung transplant ETI |
| title | Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study |
| title_full | Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study |
| title_fullStr | Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study |
| title_full_unstemmed | Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study |
| title_short | Evaluation of Elexacafor/Tezacaftor/Ivacaftor therapy after lung transplantation in Cystic Fibrosis: The Dutch National KOALA study |
| title_sort | evaluation of elexacafor tezacaftor ivacaftor therapy after lung transplantation in cystic fibrosis the dutch national koala study |
| topic | CF Lung transplant ETI |
| url | http://www.sciencedirect.com/science/article/pii/S2950133425000059 |
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