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Editorial

Drug therapies for autoimmune diseases

  • Junwei Gao ,
  • Gaolin Liu ,
Expand
  • Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20080, China
Corresponding author: Liu Gaolin, Email:

Received date: 2023-08-15

  Online published: 2024-02-22

Copyright

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Abstract

Autoimmune diseases, affecting about 10% of the world's population, have been one of the hotspots in the field of drug research because of their complex pathogenesis. The treatments for autoimmune diseases mainly include traditional synthetic disease-modifying antirheumatic drugs (DMARDs) such as glucocorticoids, immunosuppressants, immunomodulators, and anti-inflammatory drugs, macromolecular monoclonal antibodies or their derivatives such as Infliximab and Tolizumab, and small molecule targeted DMARDs such as JAK inhibitors Tofacitinib and Baritinib. The treatment of these diseases usually takes months or even years. Thus, adverse drug reaction monitoring is very important, regardless of whether they are traditional DMARDs or new biological DMARDs. For their wide range of targets, good safety, and potential role in immune regulation, natural drugs such as curcumin, resveratrol, and colquhounia root have shown good potential in the treatment of autoimmune diseases in preclinical or clinical studies.

Cite this article

Junwei Gao , Gaolin Liu . Drug therapies for autoimmune diseases[J]. Chinese Journal of Clinicians(Electronic Edition), 2023 , 17(12) : 1209 -1211 . DOI: 10.3877/cma.j.issn.1674-0785.2023.12.001

自身免疫性疾病是指免疫系统错误地攻击和破坏身体正常组织和器官的一类疾病。常见的自身免疫性疾病包括类风湿性关节炎、系统性红斑狼疮、多发性硬化症、炎症性肠病、甲状腺自身免疫疾病等。这些疾病可以影响多个器官和系统,导致炎症、组织损伤和功能障碍。自身免疫性疾病的具体原因尚不完全清楚,但遗传因素、环境因素和免疫系统失调等因素可能都起到一定的作用。治疗方法包括药物治疗、免疫调节治疗和症状缓解治疗,旨在减轻炎症、控制免疫反应和保护受影响的组织和器官。据估计,受自身免疫性疾病影响的人群约为全球总人口的10%,并有持续增加的趋势,严重影响了人民群众的身体健康,并增加了社会的经济负担1-2。由于免疫疾病的发病机制复杂,未被满足的治疗需求与潜在医疗消费仍有广阔的空间,因此仍是目前药物研发领域的热点之一。
长期以来,自身免疫疾病的治疗手段主要是依靠激素、免疫抑制剂等传统抗风湿药(disease-modifying anti-rheumatic drugs, DMARDs),治疗手段相对单一,近些年随着免疫领域研究的进展以及生物技术的突破,自身免疫性疾病的发病机制不断阐明,使得免疫领域的药物开发呈井喷式增长,出现了以肿瘤坏死因子(TNF)-α单抗为代表的生物DMARDs,和以蛋白酪氨酸激酶(JAK)抑制剂为代表的靶向DMARDs药物等新型治疗药物3。在传统医学中,具有抗炎和免疫调节作用的一些天然药物也在免疫性疾病的治疗中显示出了良好的疗效和开发前景。治疗自身免疫性疾病的药物通常分为以下几类。

一、合成DMARDs

主要包括传统的免疫抑制剂、免疫调节剂和抗炎药物:免疫抑制剂这类药物通过抑制免疫系统的活性来减少免疫系统对自身组织的攻击。常见的免疫抑制剂包括:糖皮质激素(如泼尼松)、免疫抑制剂(如环孢素、甲氨蝶呤)等;免疫调节剂:这类药物通过调节免疫系统的功能来恢复免疫系统的平衡。常见的免疫调节剂包括:硫唑嘌呤、环磷酰胺等;抗炎药物:这类药物主要用于缓解炎症反应和减轻症状。常见的抗炎药物包括:非甾体抗炎药(如布洛芬、对乙酰氨基酚)和疾病修饰抗风湿药(如甲氨蝶呤)。

二、生物DMARDs[4,5,6]

因在生物体内合成而得名,通常为大分子单克隆抗体或其衍生物,包括治疗类风湿关节炎的TNF-α抑制剂如英夫利昔单抗、白细胞介素(IL)-6抑制剂如托珠单抗、IL-1抑制剂如阿那白滞素、细胞毒性T淋巴细胞相关蛋白4(CTLA4)拮抗剂如伊匹木单抗和抗CD20药物如利妥昔单抗,治疗脊柱关节炎的IL-17抑制剂和IL-12/23抑制剂等,治疗系统性红斑狼疮的B细胞存活因子抑制剂如贝利尤单抗、Ⅰ型干扰素单克隆抗体anifrolumab等。

三、靶向DMARDs[7-8]

是指干扰细胞内信号传导和细胞因子产生的小分子靶向制剂。主要包括JAK抑制剂:针对JAK的药物,如托法替尼、巴瑞特尼等,用于治疗类风湿性关节炎、银屑病等疾病。磷酸二酯酶4抑制剂可用于银屑病和风湿性关节炎的患者,甚至是其他手段治疗无效的患者。
自身免疫性疾病的治疗通常需要数月甚至数年,药物不良反应的监测是一个不可忽视的问题,其中传统治疗药物甲氨蝶呤、硫唑嘌呤、环磷酰胺、环孢素等,多以消化道反应、骨髓抑制、肺功能损害和肝肾功能损害等不良反应为主,长期使用需监测血常规、肝肾功能等指标;糖皮质激素与非甾体抗炎药用于抗炎治疗,一般不建议长期使用,并注意监测血压、血糖、肝功能等不良反应;生物或靶向DMARDs可引起骨髓抑制、感染、胃肠道穿孔、肝功能损害等不良反应,长期使用应监测血常规、肝功能及血脂等指标。

四、天然类药物[9,10,11,12,13,14]

天然类药物由于靶点广泛、安全性好,以及在免疫调节方面的潜在作用,在自身免疫性疾病的治疗中也不可不提,以下介绍一些已用于临床或者临床试验的天然药物,可单独作为治疗药物或者作为标准治疗的辅助用药,如姜黄素、白藜芦醇、槲皮素、青藤碱(SIN)、黄芩苷、芍药苷、橙皮苷等单用或联合用于风湿性关节炎等自身免疫性疾病,可显著改善症状,且副作用更少。火把花根及其制剂在临床上用于风湿性关节炎、系统性红斑狼疮及慢性肾病等疾病的治疗中具有疗效好、毒性小的特点,显示了其在自身免疫性疾病治疗中的良好开发前景。
综上,自身免疫性疾病领域的药学研究受到了越来越多的关注,是药学研究与药物开发的重点领域之一。免疫治疗药物的市场潜力巨大,免疫疾病新靶点的药物开发,传统免疫药物以及天然药物在免疫相关疾病中的治疗价值都值得深入探讨。

利益冲突 所有作者声明不存在利益冲突

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