皮下注射贝利尤单抗治疗红斑狼疮的疗效和安全性：一项 52 周随机、双盲、安慰剂对照研究。

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty-Two-Week Randomized, Double-Blind, Placebo-Controlled Study.

机构信息

University of Southern California, Los Angeles.

Acura Kliniken Rheinland-Pfalz AG, Bad Kreuznach, Germany.

出版信息

Arthritis Rheumatol. 2017 May;69(5):1016-1027. doi: 10.1002/art.40049. Epub 2017 Apr 7.

DOI:10.1002/art.40049

PMID:28118533

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5434872/

Abstract

OBJECTIVE

To assess the efficacy and safety of subcutaneous (SC) belimumab in patients with systemic lupus erythematosus (SLE).

METHODS

Patients with moderate-to-severe SLE (score of ≥8 on the Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] version of the SLE Disease Activity Index [SLEDAI]) were randomized 2:1 to receive weekly SC belimumab 200 mg or placebo by prefilled syringe in addition to standard SLE therapy for 52 weeks. The primary end point was the SLE Responder Index (SRI4) at week 52. Secondary end points were reduction in the corticosteroid dosage and time to severe flare. Safety was assessed according to the adverse events (AEs) reported and the laboratory test results.

RESULTS

Of 839 patients randomized, 836 (556 in the belimumab group and 280 in the placebo group) received treatment. A total of 159 patients withdrew before the end of the study. At entry, mean SELENA-SLEDAI scores were 10.5 in the belimumab group and 10.3 in the placebo group. More patients who received belimumab were SRI4 responders than those who received placebo (61.4% versus 48.4%; odds ratio [OR] 1.68 [95% confidence interval (95% CI) 1.25-2.25]; P = 0.0006). In the belimumab group, both time to and risk of severe flare were improved (median 171.0 days versus 118.0 days; hazard ratio 0.51 [95% CI 0.35-0.74]; P = 0.0004), and more patients were able to reduce their corticosteroid dosage by ≥25% (to ≤7.5 mg/day) during weeks 40-52 (18.2% versus 11.9%; OR 1.65 [95% CI 0.95-2.84]; P = 0.0732), compared with placebo. AE incidence was comparable between treatment groups; serious AEs were reported by 10.8% of patients taking belimumab and 15.7% of those taking placebo. A worsening of IgG hypoglobulinemia by ≥2 grades occurred in 0.9% of patients taking belimumab and 1.4% of those taking placebo.

CONCLUSION

In patients with moderate-to-severe SLE, weekly SC doses of belimumab 200 mg plus standard SLE therapy significantly improved their SRI4 response, decreased severe disease flares as compared with placebo, and had a safety profile similar to placebo plus standard SLE therapy.

摘要

目的

评估皮下注射（SC）贝利尤单抗治疗系统性红斑狼疮（SLE）患者的疗效和安全性。

方法

将中重度 SLE 患者（SLE 疾病活动指数[SELENA]版本 SLEDAI 评分≥8 分）随机分为 2:1 组，分别接受每周一次的 SC 贝利尤单抗 200mg 或安慰剂治疗，同时给予标准 SLE 治疗，疗程 52 周。主要终点为第 52 周时的 SLE 应答指数（SRI4）。次要终点为皮质类固醇剂量减少和严重发作时间。安全性根据报告的不良事件（AE）和实验室检查结果进行评估。

结果

839 例患者随机分组，836 例（贝利尤单抗组 556 例，安慰剂组 280 例）接受治疗。共有 159 例患者在研究结束前退出。入组时，贝利尤单抗组的平均 SELENA-SLEDAI 评分为 10.5，安慰剂组为 10.3。接受贝利尤单抗治疗的患者 SRI4 应答者多于安慰剂组（61.4%比 48.4%；比值比[OR]1.68[95%置信区间（95%CI）1.25-2.25]；P=0.0006）。贝利尤单抗组的严重发作时间和风险均得到改善（中位时间 171.0 天比 118.0 天；风险比 0.51[95%CI 0.35-0.74]；P=0.0004），在第 40-52 周期间，更多患者能够减少皮质类固醇剂量≥25%（至≤7.5mg/天）（18.2%比 11.9%；OR 1.65[95%CI 0.95-2.84]；P=0.0732），与安慰剂相比。治疗组的 AE 发生率相当；接受贝利尤单抗治疗的患者中有 10.8%和安慰剂组有 15.7%报告有严重 AE。接受贝利尤单抗治疗的患者中有 0.9%和安慰剂组有 1.4%的患者出现 IgG 免疫球蛋白降低≥2 级。