Effects of lumacaftor—ivacaftor therapy on cystic fibrosis transmembrane conductance regulator function in F508del homozygous patients with cystic fibrosis aged 2-11 years
Rationale: Lumacaftor/ivacaftor was approved for the treatment of patients with cystic fibrosis who are homozygous for F508del aged 2 years and older following positive results from phase three trials. However, the improvement in CFTR function associated with lumacaftor/ivacaftor has only been studi...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
30 May 2023
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| In: |
Frontiers in pharmacology
Year: 2023, Volume: 14, Pages: 1-9 |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2023.1188051 |
| Online Access: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.3389/fphar.2023.1188051 Verlag, kostenfrei, Volltext: https://www.frontiersin.org/articles/10.3389/fphar.2023.1188051 
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| Author Notes: | Julian Berges, Simon Y. Graeber, Susanne Hämmerling, Yin Yu, Arne Krümpelmann, Mirjam Stahl, Stephanie Hirtz, Heike Scheuermann, Marcus A. Mall and Olaf Sommerburg |
| Summary: | Rationale: Lumacaftor/ivacaftor was approved for the treatment of patients with cystic fibrosis who are homozygous for F508del aged 2 years and older following positive results from phase three trials. However, the improvement in CFTR function associated with lumacaftor/ivacaftor has only been studied in patients over 12 years of age, while the rescue potential in younger children is unknown.Methods: In a prospective study, we aimed to evaluate the effect of lumacaftor/ivacaftor on the CFTR biomarkers sweat chloride concentration and intestinal current measurement as well as clinical outcome parameters in F508del homozygous CF patients 2-11 years before and 8-16 weeks after treatment initiation.Results: A total of 13 children with CF homozygous for F508del aged 2-11 years were enrolled and 12 patients were analyzed. Lumacaftor/ivacaftor treatment reduced sweat chloride concentration by 26.8 mmol/L (p = 0.0006) and showed a mean improvement in CFTR activity, as assessed by intestinal current measurement in the rectal epithelium, of 30.5% compared to normal (p = 0.0015), exceeding previous findings of 17.7% of normal in CF patients homozygous for F508del aged 12 years and older.Conclusion: Lumacaftor/ivacaftor partially restores F508del CFTR function in children with CF who are homozygous for F508del, aged 2-11 years, to a level of CFTR activity seen in patients with CFTR variants with residual function. These results are consistent with the partial short-term improvement in clinical parameters. |
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| Item Description: | Gesehen am 03.07.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2023.1188051 |