Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease
We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the <i>Phe508del</i>/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the tre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1178 |
| _version_ | 1797523780857233408 |
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| author | Vito Terlizzi Carmela Colangelo Giovanni Marsicovetere Michele D’Andria Michela Francalanci Diletta Innocenti Eleonora Masi Angelo Avarello Giovanni Taccetti Felice Amato Marika Comegna Giuseppe Castaldo Donatello Salvatore |
| author_facet | Vito Terlizzi Carmela Colangelo Giovanni Marsicovetere Michele D’Andria Michela Francalanci Diletta Innocenti Eleonora Masi Angelo Avarello Giovanni Taccetti Felice Amato Marika Comegna Giuseppe Castaldo Donatello Salvatore |
| author_sort | Vito Terlizzi |
| collection | DOAJ |
| description | We evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the <i>Phe508del</i>/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV<sub>1</sub>) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV<sub>1</sub> (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the <i>Phe508del</i> and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints. |
| first_indexed | 2024-03-10T08:47:56Z |
| format | Article |
| id | doaj.art-93de59a0b6c545f0aa1364d9a953d05e |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-93de59a0b6c545f0aa1364d9a953d05e2023-11-22T07:45:38ZengMDPI AGGenes2073-44252021-07-01128117810.3390/genes12081178Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung DiseaseVito Terlizzi0Carmela Colangelo1Giovanni Marsicovetere2Michele D’Andria3Michela Francalanci4Diletta Innocenti5Eleonora Masi6Angelo Avarello7Giovanni Taccetti8Felice Amato9Marika Comegna10Giuseppe Castaldo11Donatello Salvatore12Cystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children’s University, 50139 Florence, ItalyCystic Fibrosis Center, AOR Ospedale San Carlo, 19104 Potenza, ItalyCystic Fibrosis Center, AOR Ospedale San Carlo, 19104 Potenza, ItalyCystic Fibrosis Center, AOR Ospedale San Carlo, 19104 Potenza, ItalyCystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children’s University, 50139 Florence, ItalyCystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children’s University, 50139 Florence, ItalyCystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children’s University, 50139 Florence, ItalyInfectious and Tropical Diseases Unit, Azienda Ospedaliero-Universitaria Careggi, 50134 Florence, ItalyCystic Fibrosis Regional Reference Center, Department of Paediatric Medicine, Anna Meyer Children’s University, 50139 Florence, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples, 20122 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples, 20122 Naples, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples, 20122 Naples, ItalyCystic Fibrosis Center, AOR Ospedale San Carlo, 19104 Potenza, ItalyWe evaluated the effectiveness and safety of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in three subjects carrying the <i>Phe508del</i>/unknown CFTR genotype. An ex vivo analysis on nasal epithelial cells (NEC) indicated a significant improvement of CFTR gating activity after the treatment. Three patients were enrolled in an ELX/TEZ/IVA managed-access program, including subjects with the highest percent predicted Forced Expiratory Volume in the 1st second (ppFEV<sub>1</sub>) < 40 in the preceding 3 months. Data were collected at baseline and after 8, 12 and 24 weeks of follow-up during treatment. All patients showed a considerable decrease of sweat chloride (i.e., meanly about 60 mmol/L as compared to baseline), relevant improvement of ppFEV<sub>1</sub> (i.e., >8) and six-minute walk test, and an increase in body mass index after the first 8 weeks of treatment. No pulmonary exacerbations occurred during the 24 weeks of treatment and all domains of the CF Questionnaire-Revised improved. No safety concerns related to the treatment occurred. This study demonstrates the benefit from the ELX/TEZ/IVA treatment in patients with CF with the <i>Phe508del</i> and one unidentified CFTR variant. The preliminary ex vivo analysis of the drug response on NEC helps to predict the in vivo therapeutic endpoints.https://www.mdpi.com/2073-4425/12/8/1178elexacaftor/tezacaftor/ivacaftorcystic fibrosisCFTRnasal brushingsweat chloride |
| spellingShingle | Vito Terlizzi Carmela Colangelo Giovanni Marsicovetere Michele D’Andria Michela Francalanci Diletta Innocenti Eleonora Masi Angelo Avarello Giovanni Taccetti Felice Amato Marika Comegna Giuseppe Castaldo Donatello Salvatore Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease Genes elexacaftor/tezacaftor/ivacaftor cystic fibrosis CFTR nasal brushing sweat chloride |
| title | Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease |
| title_full | Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease |
| title_fullStr | Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease |
| title_full_unstemmed | Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease |
| title_short | Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor Therapy in Three Subjects with the Cystic Fibrosis Genotype Phe508del/Unknown and Advanced Lung Disease |
| title_sort | effectiveness of elexacaftor tezacaftor ivacaftor therapy in three subjects with the cystic fibrosis genotype phe508del unknown and advanced lung disease |
| topic | elexacaftor/tezacaftor/ivacaftor cystic fibrosis CFTR nasal brushing sweat chloride |
| url | https://www.mdpi.com/2073-4425/12/8/1178 |
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