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治疗 IgA 肾病的在研药物。

Drugs in Development to Treat IgA Nephropathy.

机构信息

Department of Nephrology and Dialysis, ASST Lariana, Como, Italy.

Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, Italy.

出版信息

Drugs. 2024 May;84(5):503-525. doi: 10.1007/s40265-024-02036-1. Epub 2024 May 23.

Abstract

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.

摘要

IgA 肾病是一种常见的肾小球肾炎,是针对异常糖基化免疫球蛋白 (Ig) A 抗体的自身免疫反应的结果。尽管它在历史上被认为是一种良性疾病,但近年来已经清楚,相当一部分患者在数年内会发展为终末期肾衰竭。已经提出了几种治疗尝试,其中全身性类固醇是最常见的,但可能存在严重的不良反应。由于对 IgA 肾病发病机制的更深入了解,已经确定了新的治疗靶点并开发了新的药物。在这篇叙述性综述中,我们总结了正在临床开发用于治疗 IgA 肾病的分子。作为一种搜索策略,我们使用了 PubMed、Google、ClinicalTrials.gov 和最近国际大会的摘要。TRF 布地奈德和 sparsentan 是两种处于更先进阶段的分子,刚刚进入市场。其他有前途的药物正在进行 III 期临床开发。这些包括抗 APRIL 和抗 BLyS/BAFF 抗体和一些补体抑制剂。其他新的可能策略包括脾酪氨酸激酶抑制剂、抗 CD40 配体和抗 CD38 抗体。在一个越来越以“个性化医学”和“精准治疗”方法为特征的时代,考虑到 IgA 肾病的潜在治疗武器库在不久的将来将非常广泛,确定能够帮助肾病学家为患者选择正确药物的生物标志物应该是未来研究的重点。

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