HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis.
HLA-DQA1∗05 Genotype and Immunogenicity to Tumor Necrosis Factor-α Antagonists: A Systematic Review and Meta-analysis.
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HLA-DQA1-05 肿瘤坏死因子-α 拮抗剂的基因型和免疫原性：系统评价和荟萃分析。
DOI：
10.1016/j.cgh.2023.03.044
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Singh,Siddharth
中科院分区：
文献类型：
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作者：
Solitano,Virginia;Facciorusso,Antonio;McGovern,DermotPB;Nguyen,Tran;Colman,RubenJ;Zou,Lily;Boland,BrigidS;Syversen,SiljeW;Jørgensen,KristinKaasen;Ma,Christopher;Armuzzi,Alessandro;Wilson,Aze;Jairath,Vipul;Singh,Siddharth
背景与目的在免疫介导的炎症性疾病（IMID）患者中选择肿瘤坏死因子（TNF）-α拮抗剂时，识别免疫原性高风险患者非常重要。我们评估了HLA-DQA 1 β 05基因型与TNF-α拮抗剂免疫原性风险之间的关系。方法通过系统回顾，截至2022年7月14日，我们确定了用TNF-α拮抗剂治疗IMID患者的研究，这些研究报告了HLA-DQA 1 β 05变异患者的免疫原性和/或继发性应答丧失风险。主要结局是免疫原性风险。采用随机效应Meta分析方法，用GRADE评价证据的可靠性。（3756例患者;中位随访时间为12个月; 41%存在变异），与非携带者相比，HLA-DQA 1 - 05变异与75%的免疫原性风险相关（相对风险，1.75; 95%置信区间，1.37-2.25），具有相当大的异质性（I2= 62%）（低确定性证据）。HLA-DQA 1105变异体预测免疫原性的阳性和阴性预测值分别为30%和80%。主动治疗药物监测，但不同时使用IMM、IMID和TNF-α拮抗剂类型，改变了这种关联。携带HLA-DQA 1/05变异体的患者发生继发性应答丧失的风险高2.2倍（6个队列;相对危险度，2.24; 95%可信区间，1.67-3.00; I2= 0%）（中等确定性证据）.结论HLA-DQA 1 β 05变异与免疫原性风险增加和接受TNF-α拮抗剂治疗的IMID患者继发性应答丧失相关。然而，阳性和阴性预测值是中等的，关于伴随使用IMM以预防免疫原性的决定应基于影响药物清除的所有因素进行个体化。
Background & AimsIdentifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor (TNF)-α antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1∗05 genotype and risk of immunogenicity with TNF-α antagonists.MethodsThrough a systematic review through July 14, 2022, we identified studies in patients with IMIDs treated with TNF-α antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1∗05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence.ResultsOn meta-analysis of 13 studies (3756 patients; median follow-up, 12 months; 41% with variants), HLA-DQA1∗05 variants were associated with 75% higher risk of immunogenicity compared with non-carriers (relative risk, 1.75; 95% confidence interval, 1.37-2.25) with considerable heterogeneity (I2= 62%) (low certainty evidence). Positive and negative predictive values of HLA-DQA1∗05 variants for predicting immunogenicity were 30% and 80%, respectively. Proactive therapeutic drug monitoring, but not concomitant use of IMMs, IMIDs, and TNF-α antagonist-type, modified this association. Patients with HLA-DQA1∗05 variants experienced 2.2-fold higher risk of secondary loss of response (6 cohorts; relative risk, 2.24; 95% confidence interval, 1.67-3.00; I2= 0%) (moderate certainty evidence).ConclusionVariants in HLA-DQA1∗05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNF-α antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.