Askanase Anca D, Furie Richard, Dall'Era Maria, Bomback Andrew S, Schwarting Andreas, Zhao Ming-Hui, Bruce Ian N, Khamashta Munther, Rubin Bernard, Carroll Angela, Levy Roger Abramino, van Vollenhoven Ronald, Urowitz Murray B
Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Division of Rheumatology, Northwell Health, Great Neck, NY, USA.
Rheumatol Ther. 2025 Jun;12(3):421-434. doi: 10.1007/s40744-025-00752-y. Epub 2025 Apr 5.
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.
随着越来越多的狼疮性肾炎（LN）药物问世，确定具有疾病改善作用的治疗方法对于做出治疗决策至关重要。根据我们2022年发表的LN疾病改善的工作定义，即“以最少的治疗相关毒性将疾病活动降至最低，并减缓进展至终末期肾病（ESKD）”，本综述的目的是根据提议的肾病改善标准对当前的LN治疗方法进行分类，不包括毒性。基于一系列LN临床试验（n = 27）和观察性研究（n = 20）的出版物，以及作者的临床经验，我们根据提议的肾病活动和器官损伤标准，在第1年、第2 - 5年以及> 5年的时间点，评估了16种LN治疗方法（包括抗疟药、糖皮质激素、免疫抑制剂、钙调神经磷酸酶抑制剂和生物制剂）的疾病改善潜力。在第1年和第2 - 5年满足标准被视为具有疾病改善潜力的证据。在> 5年时满足标准（减缓或预防系统性红斑狼疮国际协作临床/美国风湿病学会损伤指数[SDI]和ESKD的进展，和/或血清肌酐翻倍）用于确认疾病改善。每种治疗方法在每个时间点被指定为以下之一：（a）符合标准；（b）不确定；（c）无可用支持数据。本综述排除了对潜在毒性的评估。所有LN治疗方法在任何时间点都至少满足一项潜在的肾病改善标准，但文献中的相关数据有限，这意味着只有环磷酰胺的疾病改善作用能在> 5年时得到确认。贝利尤单抗在三个时间点满足的标准比任何其他生物治疗方法都多，但缺乏> 5年的数据来确认疾病改善。需要进一步研究来支持将LN治疗方法分类为疾病改善药物，特别是对于> 5年的情况。我们讨论了未来研究的考虑因素、分类面临的挑战以及对已发表标准可能的更新。
