Predictors of renal flares in systemic lupus erythematosus: a post-hoc analysis of four phase III clinical trials of belimumab.

IF 4.7 2区医学 Q1 RHEUMATOLOGY

Rheumatology Pub Date : 2025-02-01 DOI:10.1093/rheumatology/keae023

Sandra Jägerback, Alvaro Gomez, Ioannis Parodis

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引用次数: 0

Abstract

Objective: The objective of this study was to identify predictors of renal flares in patients with SLE treated for active extra-renal disease.

Methods: Data from four clinical trials of belimumab in SLE (BLISS-52, NCT00424476; BLISS-76, NCT00410384; BLISS-NEA, NCT01345253; BLISS-SC, NCT01484496) were used. Patients were assigned to belimumab or placebo on top of standard therapy. We investigated the performance of predictors of renal flares through weeks 52-76 using proportional hazards regression analysis.

Results: Of 3225 participants, 192 developed at least one renal flare during follow-up, with the first occurring after a median time of 197 days. Current/former renal involvement [hazards ratio (HR): 15.4; 95% CI: 8.3-28.2; P < 0.001], low serum albumin levels (HR 0.9; 95% CI: 0.8-0.9; P < 0.001), proteinuria (HR: 1.6; 95% CI: 1.5-1.7; P < 0.001), and low C3 levels (HR: 2.9; 95% CI: 2.1-4.1; P < 0.001) at baseline appeared robust determinants of impending renal flares. Anti-dsDNA positivity yielded an increased hazard for renal flares (HR: 2.1; 95% CI: 1.4-3.2; P < 0.001), which attenuated after adjustments. Anti-Sm positivity was associated with renal flares in the placebo (HR: 3.7; 95% CI: 2.0-6.9; P < 0.001) but not in the belimumab subgroup, whereas anti-ribosomal P positivity was associated with renal flares in the belimumab subgroup only (HR: 2.8; 95% CI: 1.5-5.0; P = 0.001).

Conclusion: A history of renal involvement, high baseline proteinuria, hypoalbuminaemia, and C3 consumption were robust determinants of impending renal flares. In addition to anti-dsDNA, anti-Sm and anti-ribosomal P protein antibody positivity may have value in surveillance of renal SLE.

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系统性红斑狼疮肾炎发作的预测因素：对四项贝利木单抗III期临床试验的事后分析。

目的确定因活动性肾外疾病而接受治疗的系统性红斑狼疮患者肾病复发的预测因素：研究采用了四项贝利木单抗治疗系统性红斑狼疮临床试验（BLISS-52，NCT00424476；BLISS-76，NCT00410384；BLISS-NEA，NCT01345253；BLISS-SC，NCT01484496）的数据。患者被分配接受贝利木单抗或安慰剂的标准治疗。我们采用比例危险回归分析法研究了52-76周肾病复发的预测因素：结果：在3225名参与者中，有192人在随访期间至少出现过一次肾病复发，首次复发的中位时间为197天。当前/既往肾脏受累（HR：15.4；95% CI：8.3-28.2；p< 0.001）、低血清白蛋白水平（HR：0.9；95% CI：0.8-0.9；p< 0.001）、蛋白尿（HR：1.6；95% CI：1.5-1.7；p< 0.001）和基线时低 C3 水平（HR：2.9；95% CI：2.1-4.1；p< 0.001）似乎是肾脏病发作的有力决定因素。抗dsDNA阳性会增加肾病复发的风险（HR：2.1；95% CI：1.4-3.2；p< 0.001），经调整后风险有所降低。在安慰剂组中，抗Sm阳性与肾炎发作有关（HR：3.7；95% CI：2.0-6.9；p< 0.001），但在贝利木单抗亚组中无关，而仅在贝利木单抗亚组中，抗核糖体P阳性与肾炎发作有关（HR：2.8；95% CI：1.5-5.0；p= 0.001）：结论：肾脏受累史、高基线蛋白尿、低白蛋白血症和C3消耗量是导致即将发生的肾病发作的重要决定因素。除抗dsDNA外，抗Sm和抗核糖体P蛋白抗体阳性可能对肾性系统性红斑狼疮的监测也有价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

7.30%

发文量

1091

审稿时长

2 months

期刊介绍： Rheumatology strives to support research and discovery by publishing the highest quality original scientific papers with a focus on basic, clinical and translational research. The journal’s subject areas cover a wide range of paediatric and adult rheumatological conditions from an international perspective. It is an official journal of the British Society for Rheumatology, published by Oxford University Press. Rheumatology publishes original articles, reviews, editorials, guidelines, concise reports, meta-analyses, original case reports, clinical vignettes, letters and matters arising from published material. The journal takes pride in serving the global rheumatology community, with a focus on high societal impact in the form of podcasts, videos and extended social media presence, and utilizing metrics such as Altmetric. Keep up to date by following the journal on Twitter @RheumJnl.