Academic Journal
Long-term impact of Elexacaftor/Tezacaftor/ivacaftor on pulmonary, nutritional and metabolic outcomes in homozygous F508del cystic fibrosis patients: A real-world cohort study.
| Τίτλος: | Long-term impact of Elexacaftor/Tezacaftor/ivacaftor on pulmonary, nutritional and metabolic outcomes in homozygous F508del cystic fibrosis patients: A real-world cohort study. |
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| Συγγραφείς: | Perrotta N; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University, Rome, Italy.; Policlinico Umberto I Hospital, Sapienza University, Rome, Italy., Fiorito LA; Department of Physiology and Pharmacology 'V. Erspamer', Sapienza University, Rome, Italy.; Policlinico Umberto I Hospital, Sapienza University, Rome, Italy., Vescovo R; Department of Chemistry and Technology of Drugs, Sapienza University, Rome, Italy., Virgilio A; Department of Chemistry and Technology of Drugs, Sapienza University, Rome, Italy., Amato G; Department of Chemistry and Technology of Drugs, Sapienza University, Rome, Italy., Cimino G; Regional Cystic Fibrosis Center, Policlinico Umberto I Hospital, Sapienza University, Rome, Italy. |
| Πηγή: | British journal of clinical pharmacology [Br J Clin Pharmacol] 2026 Jun; Vol. 92 (6), pp. 1822-1832. Date of Electronic Publication: 2026 Jan 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Wiley-Blackwell Original Publication: London, Macmillan Journals Ltd. |
| Ιατρικοί όροι (MeSH): | Cystic Fibrosis*/drug therapy , Cystic Fibrosis*/physiopathology , Cystic Fibrosis*/genetics , Cystic Fibrosis*/metabolism , Quinolones*/therapeutic use , Quinolones*/administration & dosage , Indoles*/therapeutic use , Indoles*/administration & dosage , Pyrrolidines*/therapeutic use , Pyrrolidines*/administration & dosage , Aminophenols*/therapeutic use , Aminophenols*/administration & dosage , Aminophenols*/pharmacology , Pyridines*/therapeutic use , Pyridines*/administration & dosage , Pyrazoles*/therapeutic use , Pyrazoles*/administration & dosage , Benzodioxoles*/therapeutic use, Nutritional Status/drug effects ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Lung/drug effects ; Lung/physiopathology ; Chloride Channel Agonists/therapeutic use ; Chloride Channel Agonists/administration & dosage ; Humans ; Female ; Adult ; Male ; Retrospective Studies ; Adolescent ; Young Adult ; Child ; Treatment Outcome |
| Περίληψη: | Aim: Elexacaftor/tezacaftor/ivacaftor (ETI) has markedly improved cystic fibrosis (CF) outcomes. However, its long-term impact on nutrition, metabolism and liver health remains underexplored. We assessed 30-month changes in pulmonary, nutritional, metabolic and inflammatory markers in people with CF (PwCF) homozygous for F508del. Methods: We retrospectively analysed 112 PwCF (median age-31 years) treated with ETI from July 2021 to December 2024. Clinical, spirometric and biochemical data were collected at baseline and at 6, 12, 24 and 30 months. Results: ETI produced sustained lung function gains (percent predicted FEV₁ + 15 points at 24 months, p < 0.001), BMI increase (+1.7 kg/m2 in year-one, p < 0.001) and marked C-reactive protein reduction (-80% at 6 months), with an 85% decrease in pulmonary exacerbations. Nutritional recovery shifted BMI distribution: underweight prevalence declined from 12.5% to 1.8%, while overweight rose from 15.2% to 27.7%. Adolescents improved in weight-for-age Z-scores (+0.42, p = 0.01). Total and LDL cholesterol increased but remained within reference ranges; HDL, triglycerides and glycaemic control stayed stable, with no new cystic fibrosis-related diabetes (CFRD). Vitamin D improved; vitamin B12 fluctuated with supplementation. Mild, transient transaminase elevations occurred in 4.5% of PwCF, with no fibrosis progression (APRI/FIB-4 below risk thresholds). Conclusion: ETI provides durable multisystem benefits, preserving lung function and improving nutritional and metabolic profiles. However, the shift towards overweight/obesity and biochemical signs of hepatic stress suggests evolving cardiometabolic risks. These findings support early ETI initiation and reinforce the need for ongoing monitoring of nutrition, lipid profile and liver function, together with updated CF care strategies to mitigate long-term cardiometabolic complications. (© 2026 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.) |
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| Contributed Indexing: | Keywords: Elexacaftor/Tezacaftor/ivacaftor; cystic fibrosis; inflammation; liver function; metabolic health; nutritional status |
| Substance Nomenclature: | 0 (Quinolones) 0 (Indoles) 0 (Pyrrolidines) 0 (Aminophenols) RRN67GMB0V (elexacaftor) 8RW88Y506K (tezacaftor) 0 (Pyridines) 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator) 0 (Pyrazoles) 0 (Benzodioxoles) 0 (Chloride Channel Agonists) |
| Entry Date(s): | Date Created: 20260124 Date Completed: 20260630 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13206182 |
| DOI: | 10.1002/bcp.70460 |
| PMID: | 41578635 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1365-2125 |
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| DOI: | 10.1002/bcp.70460 |