利用人类白细胞抗原基因预测炎症性肠病患者对生物疗法的耐药性。

Predicting resistance to biological therapy using human leukocyte antigen genes in patients with inflammatory bowel disease.

作者信息

Domingues Ângela, Carvalho Ana, Martinho António, Soares Caroline, Martins Diana, Sousa Paula, Araújo Ricardo, Cancela Eugénia, Silva Américo, Ministro Paula

机构信息

Department of Gastroenterology, ULS Viseu Dão Lafões, Avenida Rei Dom Duarte, Viseu 3504-509, Portugal.

Department of Gastroenterology, ULS Viseu Dão Lafões, Viseu, Portugal.

出版信息

Therap Adv Gastroenterol. 2025 Jul 11;18:17562848251353293. doi: 10.1177/17562848251353293. eCollection 2025.

DOI:10.1177/17562848251353293

PMID:40655132

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12254679/

Abstract

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-DQA105. The primary endpoint was the achievement of a composite outcome encompassing clinical, biochemical, and endoscopic remission at week 54, stratified by HLA-DQA105 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-DQA105 positive. The presence of the HLA-DQA105 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).

摘要

背景

抗肿瘤坏死因子（TNF）疗法在炎症性肠病（IBD）中的疗效常常因抗药抗体的产生而受到影响。在这种情况下，人类白细胞抗原（HLA）-DQA1*05等位基因与抗TNF药物抗药抗体的形成、反应丧失及治疗中断显著相关。

目的

我们旨在确定HLA-DQA1*05基因分型是否与IBD患者具有临床意义的结局相关。

设计

对初治生物治疗且开始使用抗TNF药物、维多珠单抗或乌司奴单抗治疗的IBD患者进行了一项单中心前瞻性研究。

方法

对所有患者进行HLA-DQA105基因分型。主要终点是在第54周实现包括临床、生化和内镜缓解的综合结局，并按HLA-DQA105状态分层。次要终点包括治疗持续性评估和抗药抗体的产生。

结果

100例初治生物治疗的IBD患者纳入研究（72例使用抗TNF药物，18例使用维多珠单抗，10例使用乌司奴单抗）；其中43%为HLA-DQA105阳性。在接受抗TNF药物、维多珠单抗或乌司奴单抗治疗的患者中，HLA-DQA105等位基因的存在与第54周临床、生化和内镜缓解综合定义的较差临床结局无关。此外，未观察到HLA-DQA1*05基因型与治疗持续性降低或免疫原性增加之间存在显著相关性。