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生物类似药背景下治疗类风湿关节炎的生物制剂、遗传学、表观遗传学与 COVID-19 治疗

Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment.

机构信息

Department of Rheumatology, National Institute of Geriatrics Rheumatology and Rehabilitation, 02-635 Warsaw, Poland.

Department of Pathophysiology and Immunology, National Institute of Geriatrics Rheumatology and Rehabilitation, 02-635 Warsaw, Poland.

出版信息

Cells. 2021 Feb 4;10(2):323. doi: 10.3390/cells10020323.

Abstract

Rheumatoid arthritis (RA) affects around 1.2% of the adult population. RA is one of the main reasons for work disability and premature retirement, thus substantially increasing social and economic burden. Biological disease-modifying antirheumatic drugs (bDMARDs) were shown to be an effective therapy especially in those rheumatoid arthritis (RA) patients, who did not adequately respond to conventional synthetic DMARD therapy. However, despite the proven efficacy, the high cost of the therapy resulted in limitation of the widespread use and unequal access to the care. The introduction of biosimilars, which are much cheaper relative to original drugs, may facilitate the achievement of the therapy by a much broader spectrum of patients. In this review we present the properties of original biologic agents based on cytokine-targeted (blockers of TNF, IL-6, IL-1, GM-CSF) and cell-targeted therapies (aimed to inhibit T cells and B cells properties) as well as biosimilars used in rheumatology. We also analyze the latest update of bDMARDs' possible influence on DNA methylation, miRNA expression and histone modification in RA patients, what might be the important factors toward precise and personalized RA treatment. In addition, during the COVID-19 outbreak, we discuss the usage of biologicals in context of effective and safe COVID-19 treatment. Therefore, early diagnosing along with therapeutic intervention based on personalized drugs targeting disease-specific genes is still needed to relieve symptoms and to improve the quality of life of RA patients.

摘要

类风湿关节炎(RA)影响约 1.2%的成年人口。RA 是导致工作能力丧失和提前退休的主要原因之一,因此大大增加了社会和经济负担。生物疾病修正抗风湿药物(bDMARDs)已被证明是一种有效的治疗方法,特别是在那些对常规合成 DMARD 治疗反应不足的类风湿关节炎(RA)患者中。然而,尽管疗效已得到证实,但治疗费用高昂导致治疗的广泛应用受限和获得治疗的机会不平等。与原药相比价格便宜得多的生物类似药的引入,可能会使更广泛的患者受益于治疗。在这篇综述中,我们介绍了基于细胞因子靶向(TNF、IL-6、IL-1、GM-CSF 抑制剂)和细胞靶向治疗(旨在抑制 T 细胞和 B 细胞特性)的原始生物制剂以及在风湿病中使用的生物类似药的特性。我们还分析了 bDMARDs 对 RA 患者 DNA 甲基化、miRNA 表达和组蛋白修饰的最新影响,这可能是实现 RA 精准和个体化治疗的重要因素。此外,在 COVID-19 爆发期间,我们讨论了生物制剂在有效和安全 COVID-19 治疗方面的应用。因此,仍需要早期诊断和基于针对疾病特异性基因的个体化药物的治疗干预,以缓解症状并改善 RA 患者的生活质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5939/7914976/29518872a481/cells-10-00323-g001.jpg

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