短期使用BG9588（抗CD40配体抗体）可改善增殖性狼疮性肾小球肾炎患者的血清学活性并减少血尿。

A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis.

作者信息

Boumpas Dimitrios T, Furie Richard, Manzi Susan, Illei Gabor G, Wallace Daniel J, Balow James E, Vaishnaw Akshay

机构信息

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

出版信息

Arthritis Rheum. 2003 Mar;48(3):719-27. doi: 10.1002/art.10856.

DOI:10.1002/art.10856

PMID:12632425

Abstract

OBJECTIVE

CD40-CD40 ligand (CD40L) interactions play a significant role in the production of autoantibodies and tissue injury in lupus nephritis. We performed an open-label, multiple-dose study to evaluate the safety, efficacy, and pharmacokinetics of BG9588, a humanized anti-CD40L antibody, in patients with proliferative lupus nephritis. The primary outcome measure was 50% reduction in proteinuria without worsening of renal function.

METHODS

Twenty-eight patients with active proliferative lupus nephritis were scheduled to receive 20 mg/kg of BG9588 at biweekly intervals for the first 3 doses and at monthly intervals for 4 additional doses. Safety evaluations were performed on all patients. Eighteen patients receiving at least 3 doses were evaluated for efficacy.

RESULTS

The study was terminated prematurely because of thromboembolic events occurring in patients in this and other BG9588 protocols (2 myocardial infarctions in this study). Of the 18 patients for whom efficacy could be evaluated, 2 had a 50% reduction in proteinuria without worsening of renal function. Mean reductions of 38.9% (P < 0.005), 50.1% (P < 0.005), and 25.3% (P < 0.05) in anti-double-stranded DNA (anti-dsDNA) antibody titers were observed at 1, 2, and 3 months, respectively, after the last treatment. There was a significant increase in serum C3 concentrations at 1 month after the last dose (P < 0.005), and hematuria disappeared in all 5 patients with significant hematuria at baseline. There were no statistically significant reductions in lymphocyte count or serum immunoglobulin, anticardiolipin antibody, or rubella IgG antibody concentrations after therapy.

CONCLUSION

A short course of BG9588 treatment in patients with proliferative lupus nephritis reduces anti-dsDNA antibodies, increases C3 concentrations, and decreases hematuria, suggesting that the drug has immunomodulatory action. Additional studies will be needed to evaluate its long-term effects.

摘要

目的

CD40 - CD40配体（CD40L）相互作用在狼疮性肾炎自身抗体产生和组织损伤中起重要作用。我们进行了一项开放标签、多剂量研究，以评估人源化抗CD40L抗体BG9588在增殖性狼疮性肾炎患者中的安全性、有效性和药代动力学。主要结局指标是蛋白尿减少50%且肾功能无恶化。

方法

28例活动性增殖性狼疮性肾炎患者计划在最初3剂时每两周接受20mg/kg的BG9588，随后4剂每月接受一次。对所有患者进行安全性评估。对18例接受至少3剂治疗的患者进行有效性评估。

结果

由于本研究及其他BG9588方案的患者发生血栓栓塞事件（本研究中有2例心肌梗死），该研究提前终止。在可评估有效性的18例患者中，2例蛋白尿减少50%且肾功能无恶化。在最后一次治疗后1、2和3个月，抗双链DNA（抗dsDNA）抗体滴度分别平均降低38.9%（P < 0.005）、50.1%（P < 0.005）和25.3%（P < 0.05）。最后一剂后1个月血清C3浓度显著升高（P < 0.005），所有5例基线时有明显血尿的患者血尿消失。治疗后淋巴细胞计数、血清免疫球蛋白、抗心磷脂抗体或风疹IgG抗体浓度均无统计学意义的降低。