Impact of HLA-DQA1*05 Genotype in Immunogenicity and Failure to Treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis (2024)

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Volume 18 Issue 7 July 2024

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Leticia Rodríguez-Alcolado

Department of Gastroenterology, Hospital General de Tomelloso

Tomelloso

Spain

Department of Public Health, Universidad de Alcalá

Alcalá de Henares

Spain

https://orcid.org/0009-0004-7394-8967

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Elena Grueso-Navarro

Department of Gastroenterology, Hospital General de Tomelloso

Tomelloso

Spain

https://orcid.org/0000-0002-5384-9978

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Ángel Arias

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd]

Madrid

Spain

Instituto de Investigación Sanitaria de Castilla

-La Mancha [IDISCAM], Toledo

Spain

Research Unit, Hospital General Mancha Centro

Alcázar de San Juan

Spain

https://orcid.org/0000-0003-1006-0958

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Alfredo J Lucendo

Department of Gastroenterology, Hospital General de Tomelloso

Tomelloso

Abstract

Background

HLA-DQA1*05 carriage has been associated with an increased risk of immunogenicity in patients with immune-mediated inflammatory diseases treated with tumour necrosis factor-alpha [TNF-a] antagonists. Results have shown an inconsistent association with a loss of response [LOR] in patients with inflammatory bowel disease [IBD], which could be modified when using proactive optimisation and association with immunomodulatory drugs.

Aims

To define the association of HLA-DQA1*05 on anti-drug antibody development and loss of response [LOR] to anti-TNF-a in IBD.

Methods

We searched MEDLINE, EMBASE, and SCOPUS, for the period up to August 2023, to identify studies reporting the risk of immunogenicity and/or LOR in IBD patients with HLA-DQA1*05 genotype.

Results

A total of 24 studies comprising 12 papers, 11 abstracts and one research letter, with a total of 5727 IBD patients, were included. In a meta-analysis of 10 studies [2984 patients; 41.9% with HLA-DQA1*05 genotype], HLA-DQA1*05 carriers had higher risk of immunogenicity compared with non-carriers (risk ratio, 1.54; 95% confidence interval [CI], 1.23 − 1.94; I² = 62%) [low certainty evidence]. Lack of therapeutic drug monitoring [TDM] increased immunogenicity in the presence of risk human leukocyte antigen [HLA] [risk ratio 1.97; 95% CI, 1.35 − 2.88; I² = 66%], whereas proactive TDM revoked this association [very low certainty of evidence]. A meta-analysis of six studies [765 patients] found that risk for secondary LOR was higher among HLA-DQA1*05 carriers [hazard ratio 2.21; 95% CI, 1.69 − 2.88; I² = 0%] [very low certainty evidence], although definition and time to assessment varied widely among studies.

Conclusion

HLA-DQA1*05 carriage may be associated with an increased risk of immunogenicity and secondary LOR in IBD patients treated with TNF-a antagonists.

Biologics, Crohn’s disease, HLA-DQA1*05, inflammatory bowel disease, pharmacogenomics, ulcerative colitis

© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/pages/standard-publication-reuse-rights)

Subject

Biomarkers

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Impact of HLA-DQA1*05 Genotype in Immunogenicity and Failure to Treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis (2024)

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