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.
J Cyst Fibros
; 2023 Oct 07.
Article
em En
| MEDLINE
| ID: mdl-37806792
ABSTRACT
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±1.4â9.8±1.2pts/p<0.001), and so had all its five domains of "pain" (16.9±2.0ptsâ9.9±1.8pts/p<0.01), "GERD" (14.4±1.8â9.9±1.6/p<0.05), "disorders of bowel movements" (19.2±1.4â14.1±1.5/p<0.01), "appetite" (7.0±1.1â4.6±1.2/p<0.01) and "impaired-QoL" (13.3±1.9â7.5±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.
Texto completo:
1
Bases de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Qualitative_research
Idioma:
En
Revista:
J Cyst Fibros
Ano de publicação:
2023
Tipo de documento:
Article