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
- PMID: 37806792
- DOI: 10.1016/j.jcf.2023.10.001
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
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±1.4→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.
Keywords: CFTR; faecal elastase; gastro-intestinal (GI); modulation; patient reported outcome measure (PROM).
Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest JGM reports independent grants and speaker/board honoraria from Vertex, Chiesi, Abbvie and Viatris outside the submitted work. CZ, FD and AB declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest PMN reports independent grants and speaker/board honoraria from Vertex outside the submitted work. JCD and her institution have received fees for Advisory Board participation, clinical trial leadership and speaking engagements from Vertex Pharmaceuticals in the field of CFTR modulators but not directly related to this study, and from AbbVie, Arcturus, Boehringer Ingelheim, Eloox, Enterprise Thearpeutics and Novartis outside the scope of this work.
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