Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial.
Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial.
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DOI：
10.1186/ar3738
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发表时间：
2012-02-07
影响因子：
4.9
通讯作者：
Singer NG
中科院分区：
文献类型：
--
作者：
Ginzler EM;Wax S;Rajeswaran A;Copt S;Hillson J;Ramos E;Singer NG
阿他西普是一种可溶的、完全人类的重组融合蛋白，可抑制B细胞刺激因子APRIL(增殖诱导配体)和BLyS(B淋巴细胞刺激因子)。这项4月-LN研究旨在评估阿西塞普在接受新启动的皮质类固醇(CS)和霉酚酸酯(MMF)治疗的活动期狼疮性肾炎(LN)患者中的有效性和安全性。这是一项随机、双盲、安慰剂对照的II/III期研究，为期52周。在筛查(第14天)时，患者开始服用大剂量的CS(0.8 mg/kg/天或60 mg/天的泼尼松)和MMF(每天1g，每周增加1g/天，至每天3g)。从第1天开始，阿替西普(150 mg，皮下注射，每周两次，连续4周，然后每周一次)开始使用MMF和逐渐减少的CS剂量。由于血清免疫球蛋白G(Ig G)的意外下降和严重感染的发生，该试验在6名患者登记后终止。因此，没有对疗效进行评估。到第1天时，与安慰剂(n=2)相比，随机服用阿昔塞普(n=4)的患者血清免疫球蛋白水平显著下降。接受阿替西普治疗的患者在第14天的蛋白尿也比服用安慰剂的患者更严重。所有患者在筛查时淋巴细胞计数都很低。阿替西普开始服药(第1天)后，免疫球蛋白G继续下降。3名接受阿昔塞特治疗的患者血清免疫球蛋白低于方案规定的停用阈值3g/L，其中两人发展为严重肺炎。需要进一步的研究来确定阿替西普在LN患者中的安全性、有效性和药效学反应。ClinicalTrials.gov：NCT00573157
Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF). This was a randomized, double-blind, placebo-controlled Phase II/III, 52-week study. At screening (Day -14), patients initiated high-dose CS (the lesser of 0.8 mg/kg/day or 60 mg/day prednisone) and MMF (1 g daily, increased by 1 g/day each week to 3 g daily). From Day 1, atacicept (150 mg, subcutaneously, twice weekly for 4 weeks, then weekly) was initiated with MMF along with a tapered dose of CS. The trial was terminated after the enrollment of six patients, due to an unexpected decline in serum immunoglobulin G (IgG) and the occurrence of serious infections. Efficacy was thus not evaluated. By Day 1, serum IgG levels had declined substantially in patients then randomized to atacicept (n = 4) compared with placebo (n = 2). Patients receiving atacicept also had more severe proteinuria on Day -14 than those on placebo. Lymphocyte counts were low at screening in all patients. IgG decline continued following initiation (Day 1) of atacicept. Three atacicept-treated patients developed serum IgG below the protocol-defined discontinuation threshold of 3 g/l, two of whom developed serious pneumonia. Future studies are needed to characterize the safety, efficacy, and pharmacodynamic response of atacicept in LN patients. ClinicalTrials.gov: NCT00573157
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