Impact of HLA-DQA1∗05 Genotype in Immunogenicity and Failure to Treatment with Tumor Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Leticia Rodríguez-Alcolado; Elena Grueso-Navarro; Ángel Arias; Alfredo J Lucendo; Emilio J Laserna-Mendieta

doi:10.1093/ecco-jcc/jjae006

Impact of HLA-DQA1∗05 Genotype in Immunogenicity and Failure to Treatment with Tumor Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

J Crohns Colitis. 2024 Jan 14:jjae006. doi: 10.1093/ecco-jcc/jjae006. Online ahead of print.

Authors

Leticia Rodríguez-Alcolado^{1

2}, Elena Grueso-Navarro¹, Ángel Arias^{3

4

5}, Alfredo J Lucendo^{1

3

4

6}, Emilio J Laserna-Mendieta^{1

4

6}

Affiliations

¹ Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain.
² Department of Surgery, Medical and Social Sciences, Universidad de Alcalá, Alcalá de Henares, Spain.
³ Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.
⁴ Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), Toledo, Spain.
⁵ Research Unit, Hospital General Mancha Centro, Alcázar de San Juan, Spain.
⁶ Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.

PMID: 38219222
DOI: 10.1093/ecco-jcc/jjae006

Abstract

Background: HLA-DQA1*05 carriage has been associated with an increased risk of immunogenicity in patients with immune-mediated inflammatory diseases treated with tumor 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 optimization 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: Twenty-four studies comprising 12 papers, 11 abstracts and 1 research letter, with a total of 5,727 IBD patients, were included. In a meta-analysis of 10 studies (2,984 patients; 41.9% with HLA-DQA1*05 genotype), HLA-DQA1*05 carriers had higher risk of immunogenicity compared to non-carriers (risk ratio, 1.54; 95%CI, 1.23-1.94; I2=62%) (low certainty evidence). Lack of therapeutic drug monitoring (TDM) increased immunogenicity in the presence of risk HLA (risk ratio 1.97; 95%CI, 1.35-2.88; I2=66%), while proactive TDM revoked this association (very low certainty of evidence). A meta-analysis of 6 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.

Keywords: Biologics; Crohn’s Disease; HLA-DQA1*05; Inflammatory bowel disease; Pharmacogenomics; Ulcerative colitis.