HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis.
Biologics
Crohn’s Disease
Pharmacogenomics
Rheumatoid Arthritis
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:
11 2023
11 2023
Historique:
received:
22
01
2023
revised:
14
03
2023
accepted:
31
03
2023
medline:
27
10
2023
pubmed:
16
4
2023
entrez:
15
4
2023
Statut:
ppublish
Résumé
Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor (TNF)-α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1∗05 genotype and risk of immunogenicity with TNF-α antagonists. Through a systematic review through July 14, 2022, we identified studies in patients with IMIDs treated with TNF-α antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1∗05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence. On meta-analysis of 13 studies (3756 patients; median follow-up, 12 months; 41% with variants), HLA-DQA1∗05 variants were associated with 75% higher risk of immunogenicity compared with non-carriers (relative risk, 1.75; 95% confidence interval, 1.37-2.25) with considerable heterogeneity (I Variants in HLA-DQA1∗05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNF-α antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.
Sections du résumé
BACKGROUND & AIMS
Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor (TNF)-α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1∗05 genotype and risk of immunogenicity with TNF-α antagonists.
METHODS
Through a systematic review through July 14, 2022, we identified studies in patients with IMIDs treated with TNF-α antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1∗05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence.
RESULTS
On meta-analysis of 13 studies (3756 patients; median follow-up, 12 months; 41% with variants), HLA-DQA1∗05 variants were associated with 75% higher risk of immunogenicity compared with non-carriers (relative risk, 1.75; 95% confidence interval, 1.37-2.25) with considerable heterogeneity (I
CONCLUSION
Variants in HLA-DQA1∗05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNF-α antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.
Identifiants
pubmed: 37061107
pii: S1542-3565(23)00270-7
doi: 10.1016/j.cgh.2023.03.044
pii:
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
HLA-DQA1 antigen
0
Tumor Necrosis Factor Inhibitors
0
Immunomodulating Agents
0
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3019-3029.e5Subventions
Organisme : NIDDK NIH HHS
ID : K23 DK117058
Pays : United States
Organisme : NIDDK NIH HHS
ID : R03 DK129631
Pays : United States
Informations de copyright
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.