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Predicting resistance to biological therapy using human leukocyte antigen genes in patients with inflammatory bowel
Ângela Domingues1, Ana Carvalho2, António Martinho3
1Department of Gastroenterology, ULS Viseu Dão Lafões, Avenida Rei Dom Duarte, Viseu 3504-509, Portugal.
Background:
The efficacy of anti-tumor necrosis factor (TNF) therapy in inflammatory bowel disease (IBD) is often compromised by the development of antidrug antibodies. In this setting, the human leukocyte antigen (HLA)-DQA1*05 allele has been significantly associated with the formation of antidrug antibodies to anti-TNF agents, loss of response, and treatment discontinuation.
Objectives:
We aimed to determine whether HLA-DQA1*05 genotyping is associated with clinically meaningful outcomes in patients with IBD.
Design:
A single-center, prospective study was conducted on patients with IBD who were naïve to biological treatment and were initiating therapy with anti-TNF agents, vedolizumab, or ustekinumab.
Methods:
All patients were genotyped for HLA-DQA1*05. The primary endpoint was the achievement of a composite outcome encompassing clinical, biochemical, and endoscopic remission at week 54, stratified by HLA-DQA1*05 status. The secondary endpoints included the evaluation of therapeutic persistence and the development of antidrug antibodies.
Results:
One hundred biologic-naïve patients with IBD initiating biological therapy were included in the study (72 on anti-TNF, 18 on vedolizumab, and 10 on ustekinumab); of these, 43% were HLA-DQA1*05 positive. The presence of the HLA-DQA1*05 allele was not associated with worse clinical outcomes, defined as the composite of clinical, biochemical, and endoscopic remission at week 54, in patients treated with anti-TNF agents, vedolizumab, or ustekinumab. In addition, no significant correlation was observed between the HLA-DQA1*05 genotype and reduced therapy persistence or increased immunogenicity.
Conclusion:
In our cohort of patients with IBD, the HLA-DQA1*05 genotype was not associated with a higher risk of treatment cessation or worse clinical outcomes.
Trial Registration:
Can we rely on HLA to predict resistance to biological therapy in patients with IBD?URL: https://clinicaltrials.gov/study/NCT05040854?cond=Can%20we%20rely%20on%20HLA&rank=1. Registration number: NCT05040854 (clinicaltrials.gov).
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