Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in Rheumatoid Arthritis Patients during the First 6 Months of Treatment with Adalimumab or Infliximab: A Descriptive Cohort Study.
Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in Rheumatoid Arthritis Patients during the First 6 Months of Treatment with Adalimumab or Infliximab: A Descriptive Cohort Study.
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抗药物抗体，药物水平，白细胞介素-6和可溶性TNF受体在类风湿关节炎患者中的前6个月中使用adalimumab或英夫利昔单抗治疗：一项描述性队列研究。
DOI：
10.1371/journal.pone.0162316
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Stoltenberg M
中科院分区：
文献类型：
--
作者：
Eng GP;Bouchelouche P;Bartels EM;Bliddal H;Bendtzen K;Stoltenberg M
在本研究中，我们希望探讨肿瘤坏死因子-α -抑制剂（TNFi）治疗对类风湿关节炎（RA）患者可溶性生物标志物水平的影响，并确定药物水平受损和抗TNFi抗体（anti-TNFi Abs）发展的预测因子。26例确诊RA患者在基线和接受阿达木单抗或英夫利昔单抗治疗6个月后采集血样。分析样本中TNFi、白细胞介素(IL)-6、可溶性tnf受体1和-2 （sTNF-R1和-2）的水平，以及抗TNFi抗体的存在。同时记录临床和人口统计学数据。在最初的6个月治疗期间，在没有抗tnfi抗体的患者和保留可检测药物水平的患者中，DAS28(CRP)（使用c反应蛋白的28个关节疾病活动评分）和IL-6和sTNF-R2水平显著下降。其他检测的细胞因子（TNF-α、TNF-β、IL-1ra、IL-1b、IL-8、IL-10、IL-12（p70）、IL-13、IL-17A、IL-17F、IL-33）水平普遍低于检测限。较高的基线水平与随访时检测不到的TNFi水平相关。抗tnfi抗体与药物水平降低有关，但未发现抗tnfi抗体发展的预测因子。TNFi治疗对RA疾病活动性的影响取决于活性药物水平和抗TNFi抗体的存在。在保留可检测药物水平的患者中，在没有抗TNFi抗体的情况下，临床结果在治疗期间得到改善，循环中IL-6和sTNF-R2水平降低。IL-6的基线水平可以预测TNFi的消耗，并可以识别有治疗失败风险的患者。
With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-α -inhibitor (TNFi) on levels of soluble biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs). Blood samples from 26 patients with established RA were taken at baseline and following 6 months of treatment with adalimumab or infliximab. Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF-receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical and demographic data were recorded as well. During the initial 6 months treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients without anti-TNFi Abs and in patients retaining detectable drug levels. The levels of other tested cytokines (TNF-α, TNF-β, IL-1ra, IL-1b, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection limits. Higher baseline levels of IL-6 associated with undetectable levels of TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but no predictors for anti-TNFi Ab development could be found. The effect of treatment with TNFi on RA disease activity depends on levels of active drug, and by presence of anti-TNFi Abs. In patients who retain detectable drug levels, and in the absence of anti-TNFi Abs, clinical outcome is improved during treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels of IL-6 may predict depletion of TNFi and may identify patients at risk of treatment failure.
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DOI：
10.1186/ar549
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Maini RN;Feldmann M
通讯作者：
Feldmann M
影响因子：
--
作者：
Mitoma, Hiroki;Horiuchi, Takahiko;Harada, Mine
通讯作者：
Harada, Mine
影响因子：
--
作者：
Schulz M;Dotzlaw H;Neeck G
通讯作者：
Neeck G
影响因子：
27.4
作者：
Bartelds, Geertje M.;Wijbrandts, Carla A.;Wolbink, Gerrit Jan
通讯作者：
Wolbink, Gerrit Jan
影响因子：
27.4
作者：
Gottenberg, Jacques-Eric;Dayer, Jean-Michel;Mariette, Xavier
通讯作者：
Mariette, Xavier