Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations
Background: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (<i>CFTR</i>) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium...
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2025-03-01
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| Series: | International Journal of Translational Medicine |
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| author | Francesca Lucca Sonia Volpi Mirco Ros Benedetta Fabrizzi Ilaria Meneghelli Marica Bordicchia Francesca Buniotto Alessia Lancini Cecilia Brignole Francesca Pauro Valentino Bezzerri Marco Cipolli |
| author_facet | Francesca Lucca Sonia Volpi Mirco Ros Benedetta Fabrizzi Ilaria Meneghelli Marica Bordicchia Francesca Buniotto Alessia Lancini Cecilia Brignole Francesca Pauro Valentino Bezzerri Marco Cipolli |
| author_sort | Francesca Lucca |
| collection | DOAJ |
| description | Background: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (<i>CFTR</i>) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium surface with thicker mucus secretions from tissues. The lungs, pancreas, liver, intestines, and sweat glands are the most common affected organs. However, pulmonary disease remains the main cause of morbidity and mortality. Fortunately, elexacaftor/tezacaftor/ivacaftor (ETI) therapy is showing unprecedented clinical benefits in patients with Cystic Fibrosis (CF) carrying at least one F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (<i>CFTR</i>) gene. However, almost 35% of the CF population living in the Mediterranean area still lacks effective CFTR modulator therapies because of the elevated incidence of patients with (pw)CF harboring <i>CFTR</i> rare mutations (RMs), different from F508del. Methods: Twenty-three pwCF harboring RM including the N1303K underwent off-label ETI treatment for 6-12 months. Respiratory function in terms of FEV1 and FVC was measured after 3, 6, and 12 months of treatment. In addition, we analyzed sweat chloride concentration, body mass index (BMI), and quality of life before and after treatment. Possible adverse effects were recorded. Results: All patients included in this off-label program displayed a substantial improvement in respiratory function. In particular, patients carrying the N1303K mutation showed an improvement in FEV1 and FVC similar to that observed in subjects harboring the F508del mutation, although sweat chloride concentration was not significantly decreased. No severe adverse effect was reported. Conclusions: This study strengthens the clinical efficacy of ETI in pwCF harboring the N1303K and other <i>CFTR</i> rare variants. Since these <i>CFTR</i> RMs have not been approved for ETI therapy in Europe, this study may promote the inclusion of these variants in the list of <i>CFTR</i> mutations responsive to ETI. |
| format | Article |
| id | doaj-art-d15e0860995740dabf9c80fc2f3d19d4 |
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| publishDate | 2025-03-01 |
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| series | International Journal of Translational Medicine |
| spelling | doaj-art-d15e0860995740dabf9c80fc2f3d19d42025-08-20T02:11:17ZengMDPI AGInternational Journal of Translational Medicine2673-89372025-03-01511110.3390/ijtm5010011Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare MutationsFrancesca Lucca0Sonia Volpi1Mirco Ros2Benedetta Fabrizzi3Ilaria Meneghelli4Marica Bordicchia5Francesca Buniotto6Alessia Lancini7Cecilia Brignole8Francesca Pauro9Valentino Bezzerri10Marco Cipolli11Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Support Center, Ca’ Foncello Hospital, 31100 Treviso, ItalyCystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, 60126 Ancona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliero Universitaria Ospedali Riuniti, 60126 Ancona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyCystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata, 37126 Verona, ItalyBackground: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (<i>CFTR</i>) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium surface with thicker mucus secretions from tissues. The lungs, pancreas, liver, intestines, and sweat glands are the most common affected organs. However, pulmonary disease remains the main cause of morbidity and mortality. Fortunately, elexacaftor/tezacaftor/ivacaftor (ETI) therapy is showing unprecedented clinical benefits in patients with Cystic Fibrosis (CF) carrying at least one F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (<i>CFTR</i>) gene. However, almost 35% of the CF population living in the Mediterranean area still lacks effective CFTR modulator therapies because of the elevated incidence of patients with (pw)CF harboring <i>CFTR</i> rare mutations (RMs), different from F508del. Methods: Twenty-three pwCF harboring RM including the N1303K underwent off-label ETI treatment for 6-12 months. Respiratory function in terms of FEV1 and FVC was measured after 3, 6, and 12 months of treatment. In addition, we analyzed sweat chloride concentration, body mass index (BMI), and quality of life before and after treatment. Possible adverse effects were recorded. Results: All patients included in this off-label program displayed a substantial improvement in respiratory function. In particular, patients carrying the N1303K mutation showed an improvement in FEV1 and FVC similar to that observed in subjects harboring the F508del mutation, although sweat chloride concentration was not significantly decreased. No severe adverse effect was reported. Conclusions: This study strengthens the clinical efficacy of ETI in pwCF harboring the N1303K and other <i>CFTR</i> rare variants. Since these <i>CFTR</i> RMs have not been approved for ETI therapy in Europe, this study may promote the inclusion of these variants in the list of <i>CFTR</i> mutations responsive to ETI.https://www.mdpi.com/2673-8937/5/1/11elexacaftor/tezacaftor/ivacaftorCFTR modulatorscystic fibrosisN1303Koff-label use |
| spellingShingle | Francesca Lucca Sonia Volpi Mirco Ros Benedetta Fabrizzi Ilaria Meneghelli Marica Bordicchia Francesca Buniotto Alessia Lancini Cecilia Brignole Francesca Pauro Valentino Bezzerri Marco Cipolli Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations International Journal of Translational Medicine elexacaftor/tezacaftor/ivacaftor CFTR modulators cystic fibrosis N1303K off-label use |
| title | Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations |
| title_full | Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations |
| title_fullStr | Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations |
| title_full_unstemmed | Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations |
| title_short | Elexacaftor/Tezacaftor/Ivacaftor Efficacy in a Cohort of Italian Patients with CFTR Rare Mutations |
| title_sort | elexacaftor tezacaftor ivacaftor efficacy in a cohort of italian patients with cftr rare mutations |
| topic | elexacaftor/tezacaftor/ivacaftor CFTR modulators cystic fibrosis N1303K off-label use |
| url | https://www.mdpi.com/2673-8937/5/1/11 |
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