PDF(Pubmed)
Abstract：
UNASSIGNED: 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-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes.
UNASSIGNED: 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.
UNASSIGNED: A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18-2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78-3.68, P < 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59-3.06, P < 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18-2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78-3.68, P < 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59-3.06, P < 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers.
UNASSIGNED: 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.
摘要：
■抗TNF治疗克罗恩病（CD）的疗效，如英夫利昔单抗，通常会因抗药物抗体（ADAs）的开发而受到损害。遗传变异HLA-DQA1*05已与生物制品的免疫原性，影响ADA的形成。本研究调查了HLA-DQA1*05与中国汉族人群中英夫利昔单抗治疗的CD患者中ADA形成之间的相关性，并评估了临床结果。
■在这项回顾性队列研究中，345例英夫利昔单抗暴露的CD患者进行HLADQA1*05A>G(rs2097432)基因分型。我们评估了ADA开发的风险，英夫利昔单抗反应丧失，不良事件,变异和野生型等位基因个体之间的治疗中断。
■与HLA-DQA1*05野生型携带者相比，在HLA-DQA1*05G变异携带者中观察到更高的ADAs形成患者百分比（58.5％vs42.9％，P=0.004)。HLA-DQA1*05携带显著增加了ADAs发生的风险（调整后的风险比=1.65，95%CI1.18-2.30，P=0.003），并且与英夫利昔单抗反应丧失的可能性更大（调整后的HR=2.55，95%CI1.78-3.68，P<0.0001）和治疗终止（调整后的HR=2.21，95%CI1.59-3.06，P<0.0001）相关有趣的是,免疫调节剂联合治疗增加了HLA-DQA1*05变异携带者的应答丢失风险.
■HLA-DQA1*05显著预测英夫利昔单抗治疗的CD患者的ADAs形成并影响治疗结果。因此，这种遗传因素的治疗前筛查可能有助于这些患者个性化抗TNF治疗策略。
■在这项回顾性队列研究中，345例英夫利昔单抗暴露的CD患者进行HLADQA1*05A>G(rs2097432)基因分型。我们评估了ADA开发的风险，英夫利昔单抗反应丧失，不良事件,变异和野生型等位基因个体之间的治疗中断。
■与HLA-DQA1*05野生型携带者相比，在HLA-DQA1*05G变异携带者中观察到更高的ADAs形成患者百分比（58.5％vs42.9％，P=0.004)。HLA-DQA1*05携带显著增加了ADAs发生的风险（调整后的风险比=1.65，95%CI1.18-2.30，P=0.003），并且与英夫利昔单抗反应丧失的可能性更大（调整后的HR=2.55，95%CI1.78-3.68，P<0.0001）和治疗终止（调整后的HR=2.21，95%CI1.59-3.06，P<0.0001）相关有趣的是,免疫调节剂联合治疗增加了HLA-DQA1*05变异携带者的应答丢失风险.
■HLA-DQA1*05显著预测英夫利昔单抗治疗的CD患者的ADAs形成并影响治疗结果。因此，这种遗传因素的治疗前筛查可能有助于这些患者个性化抗TNF治疗策略。
