Abetimus sodium for renal flare in systemic lupus erythematosus
Abetimus sodium for renal flare in systemic lupus erythematosus
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DOI：
10.1002/art.23673
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发表时间：
2008-08-01
影响因子：
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通讯作者：
Linnik, Matthew D.
中科院分区：
文献类型：
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作者：
Cardiel, Mario H.;Tumlin, James A.;Linnik, Matthew D.
目标。目的：探讨阿比莫司治疗是否能延缓狼疮性肾炎患者的肾耀斑。次要目的包括评价阿比提莫司对C3水平、抗双链DNA（抗dsdna）抗体水平、大剂量皮质类固醇和/或环磷酰胺的使用以及主要系统性红斑狼疮（SLE）发作的影响。我们对SLE患者进行了一项随机、安慰剂对照研究，以1.00 mg/周的阿贝替莫司治疗长达22个月。317例有肾炎病史且抗dsdna水平为150 IU/ml的患者被随机分为治疗组（158例阿贝地莫司，159例安慰剂）；基于基线筛查时abtimus寡核苷酸表位高亲和力抗体的存在，298（94%）入组意向治疗（ITT）人群（145例abtimus， 153例安慰剂）。阿比提莫司没有显著延长到肾发作的时间，到开始大剂量皮质类固醇和/或环磷酰胺治疗的时间，或到主要SLE发作的时间。然而，与安慰剂组相比，abtimus组的肾脏耀斑减少了25%（145例abtimus治疗患者中有17例[12%]，153例安慰剂治疗患者中有24例[16%]）。abtimus治疗降低了抗dsdna抗体水平（P < 0.0001），抗dsdna水平的降低与C3水平的升高相关（P < 0.0001）。与安慰剂组相比，abtimus组1年蛋白尿减少>= 50%的患者更多（名义P = 0.047）。在基线时肾功能受损的阿比莫司治疗的患者中，有降低肾脏耀斑和主要SLE耀斑发生率的趋势。阿贝蒂莫司治疗长达22个月，耐受性良好。与安慰剂相比，100 mg/周的Abetimus显著降低了抗dsdna抗体水平，但没有显著延长肾脏发作的时间。阿比替莫司治疗组在肾终点观察到多个阳性趋势。
Objective. To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti-double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare.Methods. We conducted a randomized, placebo-controlled study of treatment with abetimus at 1.00 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels > 15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening.Results. Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced >= 50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated.Conclusion. Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group .