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基线时前白蛋白、血小板因子 4 和 S100A12 联合预测类风湿关节炎对 TNF-α 抑制剂的良好反应。

Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response to TNF alpha inhibitors in rheumatoid arthritis.

机构信息

EA 7408, University Grenoble Alpes, GREPI, 38400 Saint-Martin-d'Hères, France; Sinnovial, 38000 Grenoble, France.

EA 7408, University Grenoble Alpes, GREPI, 38400 Saint-Martin-d'Hères, France; Rheumatology Department, centre hospitalier universitaire Grenoble Alpes, hôpital Sud Echirolles, 38130 Echirolles, France.

出版信息

Joint Bone Spine. 2019 Mar;86(2):195-201. doi: 10.1016/j.jbspin.2018.05.006. Epub 2018 Jun 6.

Abstract

OBJECTIVES

Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients.

METHODS

Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi.

RESULTS

A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually.

CONCLUSION

A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.

摘要

目的

肿瘤坏死因子-α抑制剂(TNFi)是治疗类风湿关节炎(RA)的有效方法。但治疗反应几乎无法预测。由于这些治疗方法费用高昂,并且可能引起多种副作用,我们旨在确定一组蛋白质生物标志物,可用于预测 RA 患者对 TNFi 的临床反应。

方法

在一项多中心前瞻性法国队列研究中,在开始 TNFi 治疗时,评估了 bDMARD 初治患者的基线血液 C 反应蛋白、血小板因子 4、载脂蛋白 A1、前白蛋白、α1-抗胰蛋白酶、触珠蛋白、S100A8/A9 和 S100A12 蛋白水平。在 6 个月时达到良好 EULAR 反应的患者被认为是应答者。使用逻辑回归确定最佳生物标志物组合,以预测 TNFi 的良好临床反应。

结果

确定了一种生物标志物(前白蛋白、血小板因子 4 和 S100A12)组合,可预测 RA 对 TNFi 的反应,其敏感性为 78%,特异性为 77%,阳性预测值(PPV)为 72%,阴性预测值(NPV)为 82%,阳性似然比(LR+)为 3.35,阴性似然比(LR-)为 0.28。RA 患者基线时前白蛋白和 S100A12 水平较低,血小板因子 4 水平较高,低于确定的截定点,是 TNFi 治疗以及单独使用英夫利昔单抗、依那西普和阿达木单抗反应的良好预测指标。

结论

一种结合 3 种生物标志物(前白蛋白、血小板因子 4 和 S100A12)的多变量模型可准确预测 RA 患者对 TNFi 的反应,并且在日常实践中的个性化治疗中有一定的应用潜力。

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