University of California San Francisco School of Medicine, San Francisco, California, USA.
University of California San Diego Health Sciences, La Jolla, California, USA.
Lupus Sci Med. 2024 Nov 9;11(2):e001319. doi: 10.1136/lupus-2024-001319.
High-dose glucocorticoid (GC)-based dual immunosuppressive treatment regimens are still frequently used in active lupus nephritis (LN) despite their known association with dose-dependent toxicities and incomplete efficacy. We hypothesised that the addition of voclosporin to low-dose GCs and mycophenolate mofetil (MMF) would reduce exposure to the toxicities of high-dose GC-based dual immunosuppressive therapy regimens, resulting in an improved safety profile without compromising efficacy.
Propensity score matching generated two groups of matched participants from the voclosporin arms (in combination with MMF (2 g/day) and low-dose GCs) of the Phase 2 AURA-LV and Phase 3 AURORA 1 studies and the MMF (3 g/day) and intravenous cyclophosphamide (IVC) arms (both in combination with high-dose GCs) of the Aspreva Lupus Management Study (ALMS) induction study. Safety and efficacy outcomes were assessed over 6 months.
There were 179 matched participants identified between the AURA-LV/AURORA 1 studies and ALMS. The overall incidence of adverse events (AEs) was higher in IVC- and MMF-treated participants of ALMS; more voclosporin-treated participants reported AEs by preferred term of glomerular filtration rate decreased, hypertension and anaemia. The incidence of serious AEs was similar across treatments. There were four (2.2%) deaths in IVC- and MMF-treated participants of ALMS compared with seven (3.9%) deaths in voclosporin-treated participants. Significantly more voclosporin-treated participants achieved a ≥25% reduction in urine protein creatinine ratio (UPCR) from baseline at 3 months and ≥50% reduction in UPCR from baseline at 6 months.
Compared with the high-dose GC-based regimens used in ALMS, voclosporin-based triple immunosuppressive therapy resulted in fewer AEs overall and greater and earlier reductions in proteinuria over the first 6 months of treatment. These data reinforce the feasibility of using low doses of GCs and MMF to treat LN when combined with voclosporin as a third agent.
尽管高剂量糖皮质激素（GC）为基础的双重免疫抑制治疗方案与剂量依赖性毒性和不完全疗效相关，但在活动性狼疮肾炎（LN）中仍经常使用。我们假设在低剂量 GC 和吗替麦考酚酯（MMF）的基础上添加 voclosporin 会减少与高剂量 GC 为基础的双重免疫抑制治疗方案相关的毒性暴露，从而在不影响疗效的情况下改善安全性。
从 Phase 2 AURA-LV 和 Phase 3 AURORA 1 研究的 voclosporin 组（与 MMF（2g/天）和低剂量 GC 联合使用）和 Phase 3 AURORA 1 研究的 MMF（3g/天）和静脉环磷酰胺（IVC）组（均与高剂量 GC 联合使用）中使用倾向评分匹配生成两组匹配参与者。在 6 个月内评估安全性和疗效结局。
在 AURA-LV/AURORA 1 研究和 ALMS 中，共确定了 179 名匹配参与者。ALMS 中 IVC 和 MMF 治疗参与者的不良事件（AE）总发生率较高；更多的 voclosporin 治疗参与者报告了肾小球滤过率降低、高血压和贫血的 AE 首选术语。各种治疗方法的严重 AE 发生率相似。在 ALMS 中 IVC 和 MMF 治疗参与者中有 4 例（2.2%）死亡，而 voclosporin 治疗参与者中有 7 例（3.9%）死亡。
与 ALMS 中使用的高剂量 GC 为基础的方案相比， voclosporin 为基础的三联免疫抑制治疗方案总体上导致较少的 AE，并且在治疗的前 6 个月中蛋白尿的减少更大且更早。这些数据强化了在联合使用 voclosporin 作为第三种药物时使用低剂量 GC 和 MMF 治疗 LN 的可行性。
