Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani, Rajasthan, 333 031, India.
Division of Nephrology, Department of Internal Medicine IV, Hospital of the Ludwig Maximilians University Munich, 80336, Munich, Germany.
BioDrugs. 2023 Jul;37(4):463-475. doi: 10.1007/s40259-023-00597-3. Epub 2023 Apr 24.
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), a polyclonal systemic autoimmunity directed against nuclear and other self-antigens. SLE/LN affects mostly females during childbearing age, which puts them at risk for the progression of chronic kidney disease (CKD), cardiovascular disease, and pregnancy complications. The current management of LN involves the use of drugs with significant toxicities, and despite many attempts at novel drug interventions, the overall treatment efficacy has remained low. In this article, we discuss recent drug approvals and the upcoming pipeline of novel medications tested in clinical trials to improve effectiveness in terms of LN disease activity, LN relapse, and progression of LN-related CKD. In this context, we discuss (1) drugs with the potential to achieve these treatment goals by modulating SLE activity as the driving force for LN (e.g., belimumab, obinutuzumab, anifrolumab, and others); (2) drugs with SLE-non specific renoprotective effects by targeting non-immune mechanisms of LN progression (dapagliflozin, empagliflozin); and (3) drugs with dual immunosuppressive and antiproteinuric effects (voclosporin). Increasing the number of possible drug options will help to improve the management of LN in terms of efficacy and safety, and enable a more personalized treatment approach.
狼疮性肾炎(LN)是系统性红斑狼疮(SLE)的严重并发症,是一种针对核和其他自身抗原的多克隆系统性自身免疫。SLE/LN 主要影响育龄期女性,使她们面临慢性肾脏病(CKD)、心血管疾病和妊娠并发症进展的风险。LN 的当前治疗方法涉及使用具有显著毒性的药物,尽管尝试了许多新型药物干预措施,但总体治疗效果仍然较低。在本文中,我们讨论了最近批准的药物和即将在临床试验中测试的新型药物,以提高 LN 疾病活动、LN 复发和 LN 相关 CKD 进展方面的疗效。在这方面,我们讨论了(1)通过调节作为 LN 驱动力的 SLE 活性来实现这些治疗目标的药物(例如,贝利尤单抗、奥滨尤妥珠单抗、阿尼鲁单抗等);(2)通过针对 LN 进展的非免疫机制具有 SLE 非特异性肾保护作用的药物(达格列净、恩格列净);和(3)具有双重免疫抑制和抗蛋白尿作用的药物( voclosporin)。增加可能的药物选择数量将有助于提高 LN 的治疗效果和安全性,并实现更个性化的治疗方法。