Palmer Biff F, Tumlin James A, Radhakrishnan Jai, Rehaume Linda M, Cross Jennifer L, Huizinga Robert B
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
NephroNet Clinical Research Consortium, Atlanta, GA, United States.
Front Nephrol. 2025 Mar 17;5:1540471. doi: 10.3389/fneph.2025.1540471. eCollection 2025.
Kidney injury in patients with lupus nephritis (LN) results in pro-fibrotic biomarker expression, a manifestation also observed with calcineurin inhibitor (CNI) therapy. The second-generation CNI, voclosporin, is approved in the United States and Europe for the treatment of patients with active LN in combination with background immunosuppression, based on successful outcomes from the global phase 2 AURA-LV and phase 3 AURORA 1 studies, which demonstrated the efficacy of voclosporin across diverse racial and ethnic populations, and encompassing multiple biopsy classes of LN, alongside a favorable safety profile. This analysis examined changes from baseline levels of serum and urinary biomarkers, including pro-fibrotic biomarkers, in a cohort of patients from the parent AURORA 1 study.
Samples were analyzed from a cohort of patients in AURORA 1 treated with voclosporin (23.7 mg twice daily, n=57) or placebo (n=59) in combination with mycophenolate mofetil (MMF) and low-dose glucocorticoids, including in a subgroup of patients that experienced a ≥30% decline from baseline in estimated glomerular filtration rate (voclosporin, n=26; placebo, n=20).
The addition of voclosporin to MMF and low-dose glucocorticoids for the treatment of LN did not result in significant differences in normalized urinary concentrations of KIM-1, TGF-β1, MCP-1, or NGAL, biomarkers indicative of renal fibrosis and kidney damage, when compared to MMF and low-dose glucocorticoids alone.
These findings further support the safety of voclosporin for the treatment of LN in adult patients.
ClinicalTrials.gov
狼疮性肾炎（LN）患者的肾损伤会导致促纤维化生物标志物表达，钙调神经磷酸酶抑制剂（CNI）治疗时也会出现这种表现。第二代CNI药物voclosporin已在美国和欧洲获批，可与背景免疫抑制联合用于治疗活动性LN患者。这基于全球2期AURA-LV研究和3期AURORA 1研究的成功结果，这些研究证明了voclosporin在不同种族和族裔人群中的疗效，涵盖多种活检类型的LN，且安全性良好。本分析研究了来自AURORA 1原始研究队列中患者血清和尿液生物标志物（包括促纤维化生物标志物）相对于基线水平的变化。
对AURORA 1研究中接受voclosporin（每日两次，每次23.7 mg，n = 57）或安慰剂（n = 59）联合霉酚酸酯（MMF）和低剂量糖皮质激素治疗的患者队列样本进行分析，包括估计肾小球滤过率较基线下降≥30%的患者亚组（voclosporin组，n = 26；安慰剂组，n = 20）。
与单独使用MMF和低剂量糖皮质激素相比，在MMF和低剂量糖皮质激素基础上加用voclosporin治疗LN时，肾损伤分子-1（KIM-1）、转化生长因子-β1（TGF-β1）、单核细胞趋化蛋白-1（MCP-1）或中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的标准化尿浓度无显著差异，这些生物标志物可指示肾纤维化和肾损伤。
这些发现进一步支持了voclosporin用于治疗成年LN患者的安全性。
ClinicalTrials.gov
