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优化类风湿关节炎的治疗:潜在反应生物标志物的综述。

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response.

机构信息

Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK.

出版信息

Ann Rheum Dis. 2011 Dec;70(12):2063-70. doi: 10.1136/ard.2010.148015. Epub 2011 Oct 28.

Abstract

Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.

摘要

随着对类风湿关节炎(RA)发病机制的深入了解,针对关键分子的生物制剂的出现改善了这种慢性疾病的治疗方法。尽管如此,许多患者在初始治疗后反应不佳,因此需要针对这些患者的最佳治疗方法提供指导。针对特定患者人群的研究旨在确定反应的预测生物标志物,以确定那些最有可能从特定药物治疗中获益的患者。尽管各种遗传标志物的研究结果存在矛盾,但肿瘤坏死因子(TNF)-308 启动子区域的单核苷酸多态性可能在对特定 TNF 抑制剂的反应中起作用。对 TNF 抑制剂英夫利昔单抗的反应者与无反应者的 mRNA 表达水平的微阵列分析确定了具有不同调节表达的独特基因集。在研究的各种蛋白质生物标志物中,类风湿因子和/或抗瓜氨酸蛋白自身抗体可能在预测反应或指导使用生物制剂的顺序方面具有未来的作用。需要进行更大规模、精心设计的研究,以阐明生物标志物在预测 RA 治疗反应中的作用的现有认识,以帮助指导临床决策。个体化治疗有可能改善患者的治疗效果。

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