Withdrawal of Immunomodulators or TNF Antagonists in Patients With Inflammatory Bowel Diseases in Remission on Combination Therapy: A Systematic Review and Meta-analysis.

Biologics De-escalation Immunosuppressives Safety

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:
15 Sep 2023
Historique:
received: 23 05 2023
revised: 25 07 2023
accepted: 19 08 2023
pubmed: 17 9 2023
medline: 17 9 2023
entrez: 16 9 2023
Statut: aheadofprint

Résumé

Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy. Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence. We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy. In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.

Sections du résumé

BACKGROUND & AIMS OBJECTIVE
Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy.
METHODS METHODS
Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence.
RESULTS RESULTS
We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy.
CONCLUSIONS CONCLUSIONS
In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.

Identifiants

DOI: 10.1016/j.cgh.2023.08.039 PMID: 37716619
pubmed: 37716619
pii: S1542-3565(23)00709-7
doi: 10.1016/j.cgh.2023.08.039
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

David J Katibian (DJ)

Division of Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital, San Diego, California; Department of Pediatrics, University of California, San Diego, La Jolla, California.

Virginia Solitano (V)

Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Department of Biomedical Sciences, Humanitas University, Milan, Italy.

D Brent Polk (DB)

Division of Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital, San Diego, California; Department of Pediatrics, University of California, San Diego, La Jolla, California.

Tran Nguyen (T)

Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada.

Christopher Ma (C)

Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Alimentiv Inc, London, Ontario, Canada.

Gaurav Syal (G)

Division of Gastroenterology, University of California San Diego, La Jolla, California.

Taku Kobayashi (T)

Center for Advanced IBD Research and Treatment; Kitasato University, Tokyo, Japan.

Toshifumi Hibi (T)

Center for Advanced IBD Research and Treatment; Kitasato University, Tokyo, Japan.

Sine Buhl (S)

Department of Gastroenterology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.

Mark Andrew Ainsworth (MA)

Department of Medical Gastroenterology S, Odense University Hospital, Odense, Denmark.

Vipul Jairath (V)

Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Alimentiv Inc, London, Ontario, Canada; Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada.

Siddharth Singh (S)

Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.

Classifications MeSH