MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis.

MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis.
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MRP8/14血清水平是对青少年特发性关节炎中开始和停止抗TNF治疗的反应的预测指标。

DOI:
10.1186/s13075-015-0723-1
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发表时间:
2015-08-07
影响因子:
4.9
通讯作者:
Holzinger D
Holzinger D
中科院分区:
医学2区
文献类型:
--
作者:
Anink J;Van Suijlekom-Smit LW;Otten MH;Prince FH;van Rossum MA;Dolman KM;Hoppenreijs EP;ten Cate R;Ursu S;Wedderburn LR;Horneff G;Frosch M;Vogl T;Gohar F;Foell D;Roth J;Holzinger D

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大约30%的幼年特发性关节炎(JIA)患者对抗TNF治疗无效.当诱导临床缓解时,一些患者在停止治疗后复发。我们测试了MRP 8/14血清水平的预测价值,以确定治疗的应答者和停止治疗后的复发。分析了88例开始使用TNF受体阻滞剂的非系统性JIA患者和26例停用TNF受体阻滞剂的患者的样本。在抗TNF治疗开始时、开始后6个月内和临床缓解时停用依那西普时,通过内部MRP 8/14 ELISA和Bühlmann Calprotectin ELISA测量MRP 8/14血清水平。患者在开始后6个月内被分类为应答者(ACRpedi ≥ 50和/或非活动性疾病)和无应答者(ACRpedi < 50),通过JADAS-10的变化来评估应答。在停药后6个月内评估疾病活动度。与无应答者(中位数MRP 8/14为812(IQR 570-1178),p < 0.001)相比,应答者(中位数MRP 8/14为1466 ng/ml(IQR 1045-3170))的基线MRP 8/14水平更高。治疗开始后,仅应答者的水平降低(p < 0.001)。JADAS-10的变化与基线MRP 8/14水平相关(斯皮尔曼rho 0.361,p = 0.001)。与稳定缓解患者(505 ng/ml(IQR 346-778))相比,治疗中止后6个月内发作的患者的MRP 8/14水平更高(p = 0.031,中位数1025 ng/ml(IQR 588-1288))。通过Bühlmann ELISA确认结果,具有高重现性,但总体水平不同。高水平的基线MRP 8/14与抗TNF治疗的良好反应相关,而依那西普停药时MRP 8/14水平升高与更高的发作机会相关。本文的在线版本(doi:10.1186/s13075-015-0723-1)包含补充材料,可供授权用户使用。
Approximately 30 % of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy. Samples from 88 non-systemic JIA patients who started and 26 patients who discontinued TNF-blockers were analyzed. MRP8/14 serum levels were measured by in-house MRP8/14 ELISA and by Bühlmann Calprotectin ELISA at start of anti-TNF treatment, within 6 months after start and at discontinuation of etanercept in clinical remission. Patients were categorized into responders (ACRpedi ≥ 50 and/or inactive disease) and non-responders (ACRpedi < 50) within six months after start, response was evaluated by change in JADAS-10. Disease activity was assessed within six months after discontinuation. Baseline MRP8/14 levels were higher in responders (median MRP8/14 of 1466 ng/ml (IQR 1045–3170)) compared to non-responders (median MRP8/14 of 812 (IQR 570–1178), p < 0.001). Levels decreased after start of treatment only in responders (p < 0.001). Change in JADAS-10 was correlated with baseline MRP8/14 levels (Spearman’s rho 0.361, p = 0.001). Patients who flared within 6 months after treatment discontinuation had higher MRP8/14 levels (p = 0.031, median 1025 ng/ml (IQR 588–1288)) compared to patients with stable remission (505 ng/ml (IQR 346–778)). Results were confirmed by Bühlmann ELISA with high reproducibility but different overall levels. High levels of baseline MRP8/14 are associated with good response to anti-TNF treatment, whereas elevated MRP8/14 levels at discontinuation of etanercept are associated with higher chance to flare. The online version of this article (doi:10.1186/s13075-015-0723-1) contains supplementary material, which is available to authorized users.