A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis
A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis
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DOI：
10.1016/j.kint.2018.08.025
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发表时间：
2019-01-01
影响因子：
19.6
通讯作者：
Huizinga, Robert B.
中科院分区：
文献类型：
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作者：
Rovin, Brad H.;Solomons, Neil;Huizinga, Robert B.
钙调神经磷酸酶抑制剂添加到狼疮性肾炎（LN）的标准治疗诱导治疗中可能会增加肾完全缓解（CRR）率。AURA-LV研究测试了新型钙调磷酸酶抑制剂voclosporin在活动性LN中的疗效和安全性。AURA-LV是一项2期、多中心、随机、双盲、安慰剂对照试验，比较两种剂量的voclosporin（23.7 mg或39.5 mg，每日两次）与安慰剂联合吗替麦考酚酯（2 g/d）和快速减量的低剂量口服皮质类固醇诱导LN缓解。主要终点为24周时的CRR;次要终点为48周时的CRR。招募了来自20个国家79个中心的265例受试者，并随机接受48周治疗。低剂量voclosporin组29例（32.6%）受试者、高剂量voclosporin组24例（27.3%）受试者和安慰剂组17例（19.3%）受试者在第24周达到CRR（低剂量voclosporin vs安慰剂的OR = 2.03）。低剂量voclosporin组的CRR率在48周时持续显著更高，高剂量voclosporin组的CRR在48周时也显著高于安慰剂组。与安慰剂组和高剂量voclosporin组相比，两个voclosporin组的严重不良事件更多，低剂量组的死亡人数更多（分别为11.2%，1.1%和2.3%）。这些结果表明，与单独使用吗替麦考酚酯和皮质类固醇相比，在吗替麦考酚酯和皮质类固醇的基础上加入低剂量的伏孢菌素用于活动性LN的诱导治疗，可获得上级肾反应，但观察到更高的不良事件发生率，包括死亡。
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR = 2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.