Lucia Del Vecchio, Marco Allinovi, Stefania Comolli, Silvia Peiti, Chiara Rimoldi, Francesco Locatelli
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引用次数: 0
摘要
IgA 肾病是一种常见的肾小球肾炎,由异常糖基化免疫球蛋白(Ig)A 抗体的自身免疫反应引起。尽管该病历来被认为是一种良性疾病,但多年来人们已清楚地认识到,相当比例的患者会出现终末期肾衰竭。人们提出了几种治疗方法,其中以全身性类固醇治疗最为普遍,但可能会出现严重的不良反应。随着人们对 IgA 肾病发病机制的深入了解,新的治疗目标得以确定,新的药物得以开发。在这篇叙述性综述中,我们总结了治疗 IgA 肾病的临床开发分子。作为检索策略,我们使用了 PubMed、Google、ClinicalTrials.gov 和近期国际大会的摘要。TRF 布地奈德和 sparsentan 是两种处于较先进阶段的分子,刚刚进入市场。其他前景看好的药物正在进行 III 期临床开发。这些药物包括抗 APRIL 和抗BLyS/BAFF 抗体以及一些补体抑制剂。其他可能的新策略包括脾脏酪氨酸激酶抑制剂、抗 CD40 配体和抗 CD38 抗体。在 "个性化医疗 "和 "精准治疗 "方法日益盛行的时代,考虑到 IgA 肾病的潜在治疗手段在不久的将来将非常广泛,因此,识别能够帮助肾病专家为合适的患者选择合适药物的生物标志物应成为未来研究的重点。
IgA nephropathy is a common glomerulonephritis consequent to the autoimmune response to aberrant glycosylated immunoglobulin (Ig) A antibodies. Although it has historically been considered a benign disease, it has since become clear that a substantial percentage of patients reach end-stage kidney failure over the years. Several therapeutic attempts have been proposed, with systemic steroids being the most prevalent, albeit burdened by possible serious adverse events. Thanks to the more in-depth knowledge of the pathogenesis of IgA nephropathy, new treatment targets have been identified and new drugs developed. In this narrative review, we summarise the molecules under clinical development for the treatment of IgA nephropathy. As a search strategy, we used PubMed, Google, ClinicalTrials.gov and abstracts from recent international congresses. TRF budesonide and sparsentan are the two molecules at a more advanced stage, just entering the market. Other promising agents are undergoing phase III clinical development. These include anti-APRIL and anti-BLyS/BAFF antibodies and some complement inhibitors. Other new possible strategies include spleen tyrosine kinase inhibitors, anti-CD40 ligands and anti-CD38 antibodies. In an era increasingly characterised by 'personalised medicine' and 'precision therapy' approaches and considering that the potential therapeutic armamentarium for IgA nephropathy will be very broad in the near future, the identification of biomarkers capable of helping the nephrologist to select the right drug for the right patient should be the focus of future studies.
期刊介绍:
Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes:
Leading/current opinion articles providing an overview of contentious or emerging issues.
Definitive reviews of drugs and drug classes, and their place in disease management.
Therapy in Practice articles including recommendations for specific clinical situations.
High-quality, well designed, original clinical research.
Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs.
AdisInsight Reports summarising development at first global approval.
Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.