Wang Wei, Zhang Qi, Zhao Junzhang, Liu Tao, Yao Jiayin, Peng Xiang, Zhi Min, Zhang Min
Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510655, P. R. China.
Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510655, P. R. China.
Gastroenterol Rep (Oxf). 2024 Jul 24;12:goae074. doi: 10.1093/gastro/goae074. eCollection 2024.
The efficacy of anti-TNF therapy in Crohn's disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA105 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA105 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes.
In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals.
A higher percentage of patients with ADAs formation was observed in HLA-DQA105 G variant carriers compared with HLA-DQA105 wild-type carriers (58.5% vs 42.9%, =0.004). HLA-DQA105 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18-2.30, =0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78-3.68, <0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59-3.06, <0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA105 variant carriers.
HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.
抗TNF治疗在克罗恩病（CD）中的疗效，如英夫利昔单抗，常因抗药抗体（ADA）的产生而受到影响。基因变异HLA - DQA105与生物制剂的免疫原性有关，影响ADA的形成。本研究调查了中国汉族人群中接受英夫利昔单抗治疗的CD患者HLA - DQA105与ADA形成之间的相关性，并评估临床结局。
在这项回顾性队列研究中，对345例接受英夫利昔单抗治疗的CD患者进行了HLA - DQ A1*05A G（rs2097432）基因分型。我们评估了变异型和野生型等位基因个体中ADA产生的风险、英夫利昔单抗反应丧失、不良事件和治疗中断情况。
与HLA - DQA105野生型携带者相比，HLA - DQA105 G变异型携带者中ADA形成的患者比例更高（58.5%对42.9%，=0.004）。HLA - DQA105携带显著增加了ADA产生的风险（调整后风险比=1.65，95%可信区间1.18 - 2.30，=0.003），并与英夫利昔单抗反应丧失的可能性更大相关（调整后HR = 2.55，95%可信区间1.78 - 3.68，<0.0001）以及治疗中断（调整后HR = 2.21，95%可信区间1.59 - 3.06，<0.0001）。有趣的是，免疫调节剂联合治疗增加了HLA - DQA105变异型携带者反应丧失的风险。
HLA - DQA1*05显著预测了接受英夫利昔单抗治疗的CD患者中ADA的形成，并影响治疗结局。因此，对该遗传因素进行治疗前筛查可能有助于为这些患者制定个性化的抗TNF治疗策略。
