ARD:巴瑞替尼在活动性系统性红斑狼疮患者中的作用机制及生物标志物和关键免疫通路的鉴定

2022-06-03 彼岸河边草 MedSci原创

巴瑞替尼4 mg下调了在系统性红斑狼疮患者中上调的关键细胞因子,并且可能在干扰素特征之外的多靶点机制中发挥作用。

目的为了阐明一种Janus激酶(JAK) 1/2抑制剂巴瑞替尼的作用机制,并描述在II期试验中接受标准背景治疗的系统性红斑狼疮(SLE)成人患者与疾病活动相关的免疫途径。

方法在一项II期随机、安慰剂对照研究中,SLE患者接受了2 mg4mg巴瑞替尼治疗。在基线和第12周收集了来自239名患者(巴瑞替尼2mgn=88;巴瑞替尼4mgn=82;安慰剂:n=69)和49名健康对照(HC)的血清,并使用邻近延伸实验进行分析(目标96炎症面板(Olink))。干扰素(IFN)评分是使用mRNA确定的。使用基于最大似然的受限混合模型进行重复测量,比较了SLE患者与HC患者的分析物以及巴瑞替尼2mg4mg和安慰剂组从基线到第12周时的变化。计算分析物和临床测量的Spearman 相关性。

结果在基线时,SLE血清相对于HC血清有明显的细胞因子失调。C-C基序趋化因子配体(CCL) 19C-X-C基序趋化因子配体(CXCL) 10、肿瘤坏死因子α (TNF-α)TNF受体超家族成员(TNFRSF)9/CD137PD-L1IL-6IL-12β在接受巴瑞替尼4mg 治疗的第12周患者与安慰剂相比显著降低炎症生物标志物表明IIFNCCL19CXCL10TNF-α和 PD-L1)、抗双链DNAdsDNA)(TNF -α, CXCL10) 和系统性红斑狼疮疾病活动指数-2000,关节触痛和肿胀以及最严重的关节疼痛(CCL19IL-6 TNFRSF9/CD137)相关。

结论:这些结果表明,巴瑞替尼4mg下调了在SLE患者中上调的关键细胞因子,并且可能在IFN特征之外的多靶点机制中发挥作用,尽管临床相关性仍有待进一步描述。

出处:Dörner T, Tanaka Y, Dow ER, et al. Mechanism of action of baricitinib and identification of biomarkers and key immune pathways in patients with active systemic lupus erythematosus. Annals of the Rheumatic Diseases Published Online First: 24 May 2022. doi: 10.1136/annrheumdis-2022-222335

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    2022-05-30 zhouqu_8
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