RIGOROUS DONOR SELECTION FOR FMT IN ACTIVE ULCERATIVE COLITIS: KEY LESSONS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY.

IBD Microbiome faecal microbiota transplantation ulcerative colitis

Journal

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775

Informations de publication

Date de publication:
22 May 2024
Historique:
received: 09 02 2024
revised: 03 04 2024
accepted: 02 05 2024
medline: 25 5 2024
pubmed: 25 5 2024
entrez: 24 5 2024
Statut: aheadofprint

Résumé

Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated FMT administration were hypothesized to improve FMT induction of remission in UC. The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive four anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n=72) of intended inclusions (n=108). Quantitative microbiome profiling (n=44) was performed at weeks 0 and 8. In total, 72 patients were included of which 66 received at least one FMT (allogenic-FMT n=30 and autologous-FMT n=36). At week 8, respectively 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (p=0.72), indicating no treatment difference of at least 5% in favour of allogenic-FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic-FMT compared to autologous-FMT and more transitions were observed when patients were treated with a different enterotype than their own at baseline (p=0.01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline. The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient-selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated FMT administration were hypothesized to improve FMT induction of remission in UC.
METHODS METHODS
The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive four anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n=72) of intended inclusions (n=108). Quantitative microbiome profiling (n=44) was performed at weeks 0 and 8.
RESULTS RESULTS
In total, 72 patients were included of which 66 received at least one FMT (allogenic-FMT n=30 and autologous-FMT n=36). At week 8, respectively 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (p=0.72), indicating no treatment difference of at least 5% in favour of allogenic-FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic-FMT compared to autologous-FMT and more transitions were observed when patients were treated with a different enterotype than their own at baseline (p=0.01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline.
CONCLUSION CONCLUSIONS
The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient-selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration.

Identifiants

DOI: 10.1016/j.cgh.2024.05.017 PMID: 38788915
pubmed: 38788915
pii: S1542-3565(24)00492-0
doi: 10.1016/j.cgh.2024.05.017
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Clara Caenepeel (C)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.

Sara Deleu (S)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Jorge Francisco Vazquez Castellanos (JF)

Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium.

Kaline Arnauts (K)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Sara Braekeleire (S)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Kathleen Machiels (K)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.

Filip Baert (F)

AZ Delta Roeselare, Department of Gastroenterology and Hepatology, Roeselare, Belgium.

Fazia Mana (F)

University Hospitals Brussel, Department of Gastroenterology and Hepatology, Brussel, Belgium.

Lieven Pouillon (L)

Imelda Hospital Bonheiden, Department of Gastroenterology and Hepatology, Bonheiden, Belgium.

Pieter Hindryckx (P)

Ghent University Hospital, Department of Gastroenterology, Gent, Belgium.

Triana Lobaton (T)

Ghent University Hospital, Department of Gastroenterology, Gent, Belgium; Department of Internal Medicine and Paediatrics, Ghent University, Gent, Belgium.

Edouard Louis (E)

Liège University Hospital, CHU Liège, Department of Gastroenterology and Hepatology, Liège, Belgium.

Denis Franchimont (D)

Erasmus Hospital Brussel, Department of Gastroenterology and Hepatology, Brussel, Belgium.

Bram Verstockt (B)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.

Marc Ferrante (M)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.

João Sabino (J)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium.

Sara Vieira-Silva (S)

Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Institute of Molecular Biology (IMB), Mainz, Germany.

Gwen Falony (G)

Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium; Institute of Medical Microbiology and Hygiene and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Jeroen Raes (J)

Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium.

Séverine Vermeire (S)

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; University Hospitals Leuven, Department of Gastroenterology and Hepatology, Leuven, Belgium. Electronic address: Severine.Vermeire@uzleuven.be.

Classifications MeSH