Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
Biological Products
/ adverse effects
Humans
Immunosuppressive Agents
/ adverse effects
Infections
/ chemically induced
Inflammatory Bowel Diseases
/ drug therapy
Piperidines
/ adverse effects
Protein Kinase Inhibitors
/ adverse effects
Pyrimidines
/ adverse effects
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
CD
Crohn’s Disease
UC
Ustekinumab
Vedolizumab
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:
01 2020
01 2020
Historique:
received:
08
11
2018
revised:
29
01
2019
accepted:
17
02
2019
pubmed:
17
3
2019
medline:
28
5
2021
entrez:
17
3
2019
Statut:
ppublish
Résumé
We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs). In a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs. Compared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib. Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.
Sections du résumé
BACKGROUND & AIMS
We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs).
METHODS
In a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs.
RESULTS
Compared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib.
CONCLUSIONS
Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.
Identifiants
pubmed: 30876964
pii: S1542-3565(19)30255-1
doi: 10.1016/j.cgh.2019.02.044
pmc: PMC8011651
mid: NIHMS1680859
pii:
doi:
Substances chimiques
Biological Products
0
Immunosuppressive Agents
0
Piperidines
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Tumor Necrosis Factor-alpha
0
tofacitinib
87LA6FU830
Types de publication
Comparative Study
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-81.e3Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK117058
Pays : United States
Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.
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