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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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Title: Long-term impact of Elexacaftor/Tezacaftor/ivacaftor on pulmonary, nutritional and metabolic outcomes in homozygous F508del cystic fibrosis patients: A real-world cohort study.
Authors: 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.
Source: British journal of clinical pharmacology [Br J Clin Pharmacol] 2026 Jun; Vol. 92 (6), pp. 1822-1832. Date of Electronic Publication: 2026 Jan 23.
Publication Type: Journal Article
Language: English
Journal Info: 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.
MeSH Terms: 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
Abstract: 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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Diabetes Care. 2009 Sep;32(9):1626-31. (PMID: 19542209)
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Hepatology. 2006 Jun;43(6):1317-25. (PMID: 16729309)
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
Database: MEDLINE
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  Data: 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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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.&lt;br /&gt;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.&lt;br /&gt;Results: ETI produced sustained lung function gains (percent predicted FEV₁ + 15 points at 24 months, p &amp;lt; 0.001), BMI increase (+1.7&#160;kg/m&lt;superscript&gt;2&lt;/superscript&gt; in year-one, p &amp;lt; 0.001) and marked C-reactive protein reduction (-80% at 6&#160;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).&lt;br /&gt;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.&lt;br /&gt; (&#169; 2026 The Author(s). British Journal of Clinical Pharmacology published by John Wiley &amp; Sons Ltd on behalf of British Pharmacological Society.)
– Name: Ref
  Label: References
  Group: RefInfo
  Data: J Cyst Fibros. 2025 Jul;24(4):801-808. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2239956715%22&quot;&gt;39956715)&lt;/searchLink&gt;&lt;br /&gt;Diabetes Care. 2009 Sep;32(9):1626-31. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2219542209%22&quot;&gt;19542209)&lt;/searchLink&gt;&lt;br /&gt;Diabetes Care. 2010 Dec;33(12):2697-708. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2221115772%22&quot;&gt;21115772)&lt;/searchLink&gt;&lt;br /&gt;Hepatology. 2024 May 1;79(5):1220-1238. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2237934656%22&quot;&gt;37934656)&lt;/searchLink&gt;&lt;br /&gt;Eur Respir J. 2023 Apr 1;61(4):. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2236265882%22&quot;&gt;36265882)&lt;/searchLink&gt;&lt;br /&gt;JCI Insight. 2024 Feb 15;9(6):. (PMID: &lt;searchLink fieldCode=&quot;PM&quot; term=&quot;%2238358827%22&quot;&gt;38358827)&lt;/searchLink&gt;&lt;br /&gt;JPGN Rep. 2025 Mar 17;6(2):146-152. 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  Label: Contributed Indexing
  Group:
  Data: &lt;i&gt;Keywords: &lt;/i&gt;Elexacaftor/Tezacaftor/ivacaftor; cystic fibrosis; inflammation; liver function; metabolic health; nutritional status
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (Quinolones)&lt;br /&gt;0 (Indoles)&lt;br /&gt;0 (Pyrrolidines)&lt;br /&gt;0 (Aminophenols)&lt;br /&gt;RRN67GMB0V (elexacaftor)&lt;br /&gt;8RW88Y506K (tezacaftor)&lt;br /&gt;0 (Pyridines)&lt;br /&gt;126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)&lt;br /&gt;0 (Pyrazoles)&lt;br /&gt;0 (Benzodioxoles)&lt;br /&gt;0 (Chloride Channel Agonists)
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  Label: Entry Date(s)
  Group: Date
  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260124 &lt;i&gt;Date Completed: &lt;/i&gt;20260630 &lt;i&gt;Latest Revision: &lt;/i&gt;20260813
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  Label: Update Code
  Group: Date
  Data: 20260813
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  Label: PubMed Central ID
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  Data: PMC13206182
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1002/bcp.70460
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  Data: 41578635
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=41578635
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      – Type: doi
        Value: 10.1002/bcp.70460
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      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 1822
    Subjects:
      – SubjectFull: Nutritional Status drug effects
        Type: general
      – SubjectFull: Cystic Fibrosis Transmembrane Conductance Regulator genetics
        Type: general
      – SubjectFull: Lung drug effects
        Type: general
      – SubjectFull: Lung physiopathology
        Type: general
      – SubjectFull: Chloride Channel Agonists therapeutic use
        Type: general
      – SubjectFull: Chloride Channel Agonists administration & dosage
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Retrospective Studies
        Type: general
      – SubjectFull: Adolescent
        Type: general
      – SubjectFull: Young Adult
        Type: general
      – SubjectFull: Child
        Type: general
      – SubjectFull: Treatment Outcome
        Type: general
      – SubjectFull: Cystic Fibrosis drug therapy
        Type: general
      – SubjectFull: Cystic Fibrosis physiopathology
        Type: general
      – SubjectFull: Cystic Fibrosis genetics
        Type: general
      – SubjectFull: Cystic Fibrosis metabolism
        Type: general
      – SubjectFull: Quinolones therapeutic use
        Type: general
      – SubjectFull: Quinolones administration & dosage
        Type: general
      – SubjectFull: Indoles therapeutic use
        Type: general
      – SubjectFull: Indoles administration & dosage
        Type: general
      – SubjectFull: Pyrrolidines therapeutic use
        Type: general
      – SubjectFull: Pyrrolidines administration & dosage
        Type: general
      – SubjectFull: Aminophenols therapeutic use
        Type: general
      – SubjectFull: Aminophenols administration & dosage
        Type: general
      – SubjectFull: Aminophenols pharmacology
        Type: general
      – SubjectFull: Pyridines therapeutic use
        Type: general
      – SubjectFull: Pyridines administration & dosage
        Type: general
      – SubjectFull: Pyrazoles therapeutic use
        Type: general
      – SubjectFull: Pyrazoles administration & dosage
        Type: general
      – SubjectFull: Benzodioxoles therapeutic use
        Type: general
    Titles:
      – TitleFull: Long-term impact of Elexacaftor/Tezacaftor/ivacaftor on pulmonary, nutritional and metabolic outcomes in homozygous F508del cystic fibrosis patients: A real-world cohort study.
        Type: main
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            NameFull: Perrotta N
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            NameFull: Fiorito LA
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            NameFull: Vescovo R
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            NameFull: Amato G
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          Dates:
            – D: 01
              M: 06
              Text: 2026 Jun
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1365-2125
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              Value: 92
            – Type: issue
              Value: 6
          Titles:
            – TitleFull: British journal of clinical pharmacology
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