Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.
Division of Rheumatology, Northwell Health, Great Neck, New York, USA.
Lupus Sci Med. 2024 May 22;11(1):e001124. doi: 10.1136/lupus-2023-001124.
Our 2022 published working definition of disease modification in systemic lupus erythematosus (SLE) was 'minimising disease activity with the fewest treatment-associated toxicities and slowing or preventing organ damage progression'. The objective of this review was to classify current SLE treatments according to the proposed non-renal disease modification criteria excluding toxicities. Based on a review of select clinical trial (n=32) and observational study (n=54) publications for 14 SLE medications across different therapeutic classes, and the authors' clinical experience, we evaluated disease modification potential as per the proposed framework at three time points. Specific criteria used to determine disease modification potential included a drug's capacity to reduce: (1) non-renal disease activity, (2) severe flares, (3) use of steroids/immunosuppressants and (4) organ damage accrual. Criteria 1-3 were assessed at 1 year and 2-5 years and, when positive, were considered evidence for disease modification potential; criterion 4 was used to confirm disease modification at >5 years. Each treatment received one of four mutually exclusive designations at each time point: (a) criterion met, (b) indications of criterion met despite insufficient evidence in the literature, (c) inconclusive and (d) no available supportive data. This review excludes an assessment of potential toxicities. Eight of the 14 SLE treatments met ≥1 disease modification criteria up to year 5. Hydroxychloroquine improved overall survival at >5 years, suggesting long-term disease modification, but no data on specific organ systems were reported. Belimumab was the only treatment to meet all criteria. Belimumab and hydroxychloroquine met disease modification definitions across three time points. Evidence for other SLE therapies was incomplete, particularly at >5 years. Future studies are warranted for other treatments to meet the disease modification criteria. We discuss challenges to classification and possible updates to our published criteria.
我们在 2022 年发表的系统性红斑狼疮(SLE)疾病修饰治疗的定义为“用最少的治疗相关毒性最小化疾病活动度并减缓或预防器官损伤进展”。本综述的目的是根据提出的不包括毒性的非肾脏疾病修饰标准,对当前的 SLE 治疗方法进行分类。基于对 14 种不同治疗类别的 SLE 药物的选择性临床试验(n=32)和观察性研究(n=54)出版物的审查,以及作者的临床经验,我们根据提出的框架在三个时间点评估了疾病修饰潜力。用于确定疾病修饰潜力的具体标准包括药物减少以下方面的能力:(1)非肾脏疾病活动度,(2)严重发作,(3)使用类固醇/免疫抑制剂,(4)器官损伤积累。标准 1-3 在 1 年和 2-5 年进行评估,如果为阳性,则认为具有疾病修饰潜力;标准 4 用于在>5 年时确认疾病修饰。每种治疗方法在每个时间点都有以下四个相互排斥的指定之一:(a)符合标准,(b)尽管文献中证据不足,但符合标准的迹象,(c)不确定,(d)无可用支持数据。本综述不包括对潜在毒性的评估。在 5 年内,有 8 种 SLE 治疗方法符合≥1 种疾病修饰标准。羟氯喹在>5 年内改善了总生存率,表明长期疾病修饰,但未报告特定器官系统的数据。贝利木单抗是唯一符合所有标准的治疗方法。贝利木单抗和羟氯喹在三个时间点都符合疾病修饰定义。其他 SLE 疗法的证据不完整,特别是在>5 年内。其他治疗方法需要进行更多的研究以符合疾病修饰标准。我们讨论了分类的挑战和我们发表的标准的可能更新。