Disease-Modifying Therapies in Lupus Nephritis: A Narrative Review Evaluating Currently Used Pharmacologic Agents.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2025-04-05 DOI:10.1007/s40744-025-00752-y

Anca D Askanase, Richard Furie, Maria Dall'Era, Andrew S Bomback, Andreas Schwarting, Ming-Hui Zhao, Ian N Bruce, Munther Khamashta, Bernard Rubin, Angela Carroll, Roger Abramino Levy, Ronald van Vollenhoven, Murray B Urowitz

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Abstract

As more lupus nephritis (LN) medications become available, identifying treatments that are disease-modifying is critical in making treatment decisions. Based on our 2022 published working definition of LN disease modification as 'minimizing disease activity with the fewest treatment-associated toxicities and slowing progression to end-stage kidney disease' (ESKD), the objective of this review was to classify current LN treatments according to the proposed kidney disease modification criteria, excluding toxicities. Based upon a selection of LN clinical trial (n = 27) and observational study (n = 20) publications, as well as the authors' clinical experiences, we evaluated the disease modification potential for 16 LN treatments (inclusive of antimalarials, glucocorticoids, immunosuppressants, calcineurin inhibitors and biologics) according to the proposed kidney disease activity and organ damage criteria at year 1, years 2-5, and > 5-year time points. Fulfilling criteria at year 1 and years 2-5 was considered evidence for disease modification potential. Satisfying criteria at > 5 years (slowing or preventing progression in SLICC/ACR Damage Index [SDI] and ESKD, and/or doubling of serum creatinine) was used to confirm disease modification. Each treatment was designated as one of the following at each time point: (a) criterion met; (b) inconclusive; (c) no available supportive data. This review excluded an assessment of potential toxicities. All LN treatments met at least one of the potential kidney disease-modification criteria at any time point, but limited relevant data in the literature meant disease modification > 5 years could only be confirmed for cyclophosphamide. Belimumab met more criteria across the three time points than any other biologic treatment but lacked > 5-year data to confirm disease modification. Further research is needed to support the classification of LN treatments as disease modifiers, particularly for > 5 years. We discuss considerations for future studies, challenges to the classification, and possible updates to published criteria.

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狼疮性肾炎的疾病改善疗法：评价目前使用的药物的叙述性综述。

随着越来越多的狼疮肾炎（LN）药物的出现，确定能够改善疾病的治疗方法对于做出治疗决定至关重要。基于我们2022年发布的LN疾病修饰的工作定义，即“以最少的治疗相关毒性最小化疾病活动性，减缓终末期肾脏疾病的进展”（ESKD），本综述的目的是根据拟议的肾脏疾病修饰标准对当前LN治疗进行分类，不包括毒性。基于LN临床试验（n = 27）和观察性研究（n = 20）出版物的选择，以及作者的临床经验，我们根据建议的肾脏疾病活动性和器官损害标准，在1年、2-5年和5- 5年的时间点，评估了16种LN治疗（包括抗疟药、糖皮质激素、免疫抑制剂、钙调磷酸酶抑制剂和生物制剂）的疾病改变潜力。在第1年和第2-5年达到标准被认为是疾病改变潜力的证据。满足bbb50年的标准（减缓或防止SLICC/ACR损伤指数[SDI]和ESKD的进展，和/或血清肌酐加倍）用于确认疾病改善。在每个时间点，每种治疗被指定为以下一种：(a)满足标准；(b)不确定;(c)没有可用的支持性数据。本综述排除了对潜在毒性的评估。在任何时间点，所有LN治疗都至少满足一项潜在的肾脏疾病改善标准，但文献中有限的相关数据意味着只有环磷酰胺治疗才能确认5年的疾病改善。在三个时间点上，贝利单抗比其他任何生物治疗都符合更多的标准，但缺乏bbb10年的数据来证实疾病的改善。需要进一步的研究来支持LN治疗作为疾病调节剂的分类，特别是50年。我们讨论了对未来研究的考虑，对分类的挑战，以及对已公布标准的可能更新。

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies. 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At least two extensive reviews are required to make the editorial decision. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments if appropriate. 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