Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and Calprotectin over one year of treatment with Elexacaftor-Tezacaftor-Ivacaftor in people with CF aged ≥12 years - The RECOVER study
Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved..
BACKGROUND: RECOVER is a multicentre post-approval study of Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pwCF in Ireland and the UK. The CFAbd-Score is the first validated CF-specific patient reported outcome measure (PROM) focusing on gastrointestinal symptoms; it comprises 28 items in 5 domains. In a preliminary study, we previously reported reductions in abdominal symptoms (AS) in pwCF after 26 weeks of ETI-therapy using the CFAbd-Score.
AIM: to assess changes in AS in a second, large cohort and explore novel GI-biomarkers of gut inflammation and cell-proliferation in pwCF over one year of ETI-therapy.
METHODS: Participants were recruited as part of the RECOVER study at 8 sites (Ireland&UK). The CFAbd-Score was administered prior to ETI-initiation, and subsequently at 1,2,6 and 12 months on treatment. Faecal M2-pyruvate kinase (M2-PK) and calprotectin (FC) were quantified in samples collected at baseline, 1 and 6 months.
RESULTS: 108 CFAbd-Scores and 73 stool samples were collected at baseline. After 12 months of ETI-therapy, total CFAbd-Scores had significantly declined (15.0±1.4→9.8±1.2pts/p<0.001), and so had all its five domains of "pain" (16.9±2.0pts→9.9±1.8pts/p<0.01), "GERD" (14.4±1.8→9.9±1.6/p<0.05), "disorders of bowel movements" (19.2±1.4→14.1±1.5/p<0.01), "appetite" (7.0±1.1→4.6±1.2/p<0.01) and "impaired-QoL" (13.3±1.9→7.5±1.5/p<0.001). Levels of M2-PK and FC significantly decreased during ETI-therapy.
DISCUSSION: In-depth analysis of AS with the CFAbd-Score reveals a statistically significant, clinically relevant and sustained improvement with ETI. We attribute this to high sensitivity of the implemented CF-specific PROM, developed and validated following FDA-guidelines. Furthermore, for the first time during ETI-therapy a significant decline in faecal M2-PK, a marker of inflammation and cell-proliferation, was found, in parallel to FC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society - (2023) vom: 07. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mainz, Jochen G [VerfasserIn] |
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| Links: |
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| Themen: |
CFTR |
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| Anmerkungen: |
Date Revised 08.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.jcf.2023.10.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363003827 |
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| 100 | 1 | |a Mainz, Jochen G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and Calprotectin over one year of treatment with Elexacaftor-Tezacaftor-Ivacaftor in people with CF aged ≥12 years - The RECOVER study |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 08.10.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: RECOVER is a multicentre post-approval study of Elexacaftor/Tezacaftor/Ivacaftor (ETI) in pwCF in Ireland and the UK. The CFAbd-Score is the first validated CF-specific patient reported outcome measure (PROM) focusing on gastrointestinal symptoms; it comprises 28 items in 5 domains. In a preliminary study, we previously reported reductions in abdominal symptoms (AS) in pwCF after 26 weeks of ETI-therapy using the CFAbd-Score | ||
| 520 | |a AIM: to assess changes in AS in a second, large cohort and explore novel GI-biomarkers of gut inflammation and cell-proliferation in pwCF over one year of ETI-therapy | ||
| 520 | |a METHODS: Participants were recruited as part of the RECOVER study at 8 sites (Ireland&UK). The CFAbd-Score was administered prior to ETI-initiation, and subsequently at 1,2,6 and 12 months on treatment. Faecal M2-pyruvate kinase (M2-PK) and calprotectin (FC) were quantified in samples collected at baseline, 1 and 6 months | ||
| 520 | |a RESULTS: 108 CFAbd-Scores and 73 stool samples were collected at baseline. After 12 months of ETI-therapy, total CFAbd-Scores had significantly declined (15.0±1.4→9.8±1.2pts/p<0.001), and so had all its five domains of "pain" (16.9±2.0pts→9.9±1.8pts/p<0.01), "GERD" (14.4±1.8→9.9±1.6/p<0.05), "disorders of bowel movements" (19.2±1.4→14.1±1.5/p<0.01), "appetite" (7.0±1.1→4.6±1.2/p<0.01) and "impaired-QoL" (13.3±1.9→7.5±1.5/p<0.001). Levels of M2-PK and FC significantly decreased during ETI-therapy | ||
| 520 | |a DISCUSSION: In-depth analysis of AS with the CFAbd-Score reveals a statistically significant, clinically relevant and sustained improvement with ETI. We attribute this to high sensitivity of the implemented CF-specific PROM, developed and validated following FDA-guidelines. Furthermore, for the first time during ETI-therapy a significant decline in faecal M2-PK, a marker of inflammation and cell-proliferation, was found, in parallel to FC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CFTR | |
| 650 | 4 | |a faecal elastase | |
| 650 | 4 | |a gastro-intestinal (GI) | |
| 650 | 4 | |a modulation | |
| 650 | 4 | |a patient reported outcome measure (PROM) | |
| 700 | 1 | |a Lester, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Elnazir, Basil |e verfasserin |4 aut | |
| 700 | 1 | |a Williamson, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a McKone, Ed |e verfasserin |4 aut | |
| 700 | 1 | |a Cox, Des |e verfasserin |4 aut | |
| 700 | 1 | |a Linnane, Barry |e verfasserin |4 aut | |
| 700 | 1 | |a Zagoya, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Duckstein, Franziska |e verfasserin |4 aut | |
| 700 | 1 | |a Barucha, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Davies, Jane C |e verfasserin |4 aut | |
| 700 | 1 | |a McNally, Paul |e verfasserin |4 aut | |
| 700 | 0 | |a RECOVER Study Group |e verfasserin |4 aut | |
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