在炎症性肠病中,HLA-DQA1*05等位基因携带和抗TNF治疗的持续性
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Jayne Doherty1,2,3, Anthony W Ryan4, Emma Quinn4
1Gastroenterology Department, St James's Hospital, Dublin, Ireland.
Inflammatory bowel diseases
|June 28, 2024
概括
具有两个副本HLA-DQA1*05等位基因的患者经历了较短的抗瘤坏死因子 (抗TNF) 治疗持续时间. 这一发现表明HLA-DQA1*05基因型可能会为炎症性肠病的治疗选择提供信息.
科学领域:
- 遗传学和免疫学 遗传学和免疫学
- 胃肠病学 胃肠病学
- 药物基因组学 药物基因组学
背景情况:
- 在克罗恩病中,HLA-DQA1*05等位基因与抗药抗体 (ADA) 与抗瘤坏死因子 (anti-TNF) 疗法有关.
- 然而,ADA并不总是与治疗失败相关,因此需要进一步研究预测因素.
研究的目的:
- 研究HLA-DQA1*05基因携带对生物治疗结果的影响,特别关注药物持续性.
- 开发一种针对抗TNF治疗失败的预测风险评分,其中包括HLA-DQA1*05基因型.
主要方法:
- 一项多中心的回顾性研究,涉及877名患有炎症性肠病 (IBD) 的患者,正在接受抗TNF治疗.
- 使用全基因组测序归算 (R中的HIBAG) 进行了HLA-DQA1*05基因型鉴定.
- 主要终点是抗TNF治疗的持续性,通过HLA-DQA1*05基因型状态和发达风险评分 (LORisk评分) 来分析.
主要成果:
- 拥有两个副本HLA-DQA1*05的患者与零 (541天) 或一个副本 (513天) (P=.012) 的患者相比,抗TNF治疗失败的平均时间 (418天) 显著缩短 (P=.012).
- 与治疗失败相关的独立因素包括HLA-DQA1*05携带 (HR 1.2,P=.02),女性性别 (HR 1.6,P<.001),UC表型 (HR 1.4,P=.009),以及因弗力西马布治疗 (HR 1.5,P=.002).
- 洛里斯克得分显著预测到抗TNF治疗失败的时间更短 (P<.001).
结论:
- 携带两个HLA-DQA1*05等位基因与接受抗TNF治疗的患者的不太有利的结果和更短的治疗持续时间有关.
- 将HLA-DQA1*05基因型状态与临床因素结合起来,可能有助于优化IBD患者的治疗选择.
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