Schiotis Ruxandra, Sánchez Alejandra, Escudero Alejandro, Bartolomé Nerea, Szczypiorska Magdalena, Font Pilar, Martínez Antonio, Tejedor Diego, Artieda Marta, Mulero Juan, Buzoianu Anca, Collantes-Estévez Eduardo
Department of Pharmacology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania,
Rheumatol Int. 2014 Jun;34(6):793-801. doi: 10.1007/s00296-013-2913-y. Epub 2013 Dec 15.
The objective of this study is to identify single-nucleotide polymorphisms (SNPs) predictors of treatment nonresponse to the first anti-TNF-alpha agent in ankylosing spondylitis (AS). Patients were classified as "nonresponders" if they failed to achieve improvement ≥50 % of the initial BASDAI. We selected candidate SNPs previously reported, associated with susceptibility or pathogenesis of AS and with other spondylarthropaties (SpAs). The predictors of nonresponse were modeled with multiple logistic regression. The predictive power of the genetic model of nonresponse to treatment was tested with AUC-ROC. One hundred and twenty-one (121) AS patients fulfilled the inclusion criteria. Of the candidate SNPs tested for association with treatment effectiveness, five independent predictors were identified: rs917997, rs755622, rs1800896, rs3740691, and rs1061622. The genetic model of nonresponse to treatment had a predictive power of 0.77 (95 % CI 0.68-0.86). Our study identified several polymorphisms which could be the useful genetic biomarkers in predicting nonresponse to anti-TNF-alpha therapy.
本研究的目的是确定强直性脊柱炎（AS）患者对第一种抗TNF-α药物治疗无反应的单核苷酸多态性（SNP）预测因子。如果患者未能使初始巴斯强直性脊柱炎疾病活动指数（BASDAI）改善≥50%，则被归类为“无反应者”。我们选择了先前报道的与AS易感性或发病机制以及其他脊柱关节炎（SpA）相关的候选SNP。使用多元逻辑回归对无反应的预测因子进行建模。用受试者工作特征曲线下面积（AUC-ROC）检验治疗无反应遗传模型的预测能力。121例AS患者符合纳入标准。在检测与治疗效果相关的候选SNP中，确定了五个独立预测因子：rs917997、rs755622、rs1800896、rs3740691和rs1061622。治疗无反应的遗传模型预测能力为0.77（95%置信区间0.68-0.86）。我们的研究确定了几种多态性，它们可能是预测抗TNF-α治疗无反应的有用遗传生物标志物。
