Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA.
Clin Ther. 2012 May;34(5):1006-22. doi: 10.1016/j.clinthera.2012.02.028. Epub 2012 Mar 30.
Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA).
This article reviews the current research on belimumab and provides recommendations on its use in the treatment of SLE.
The Cochrane Library, EBSCO, IPA, MEDLINE, and SCOPUS were searched for research published from January 2000 to November 2011, using the search terms belimumab, Benlysta, and Lympho-Stat B. Selection criteria included peer-reviewed original research articles on the pharmacology, pharmacokinetic properties, drug interactions, and clinical efficacy and tolerability of belimumab in the treatment of SLE. Abstracts from the annual meetings of major rheumatology medical organizations and societies were searched and reviewed for new content. Additional information on belimumab was obtained from the manufacturer, from the FDA, and from other sources. MEDLINE was also used to select clinical studies and therapeutic guidelines on SLE therapy.
The literature search identified 1 Phase II and 2 Phase III studies that compared belimumab (1, 4, and 10 mg/kg/dose IV on days 0, 14, and 28; then every 28 days) to placebo in patients with active SLE on concurrent therapies. Patients with active lupus nephritis or neuropsychiatric lupus were excluded. In a Phase II, 52-week study, 24-week mean Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores were decreased by 19.5% with belimumab versus 17.2% with placebo (P = NS). Median time to first flare was 67 days with belimumab versus 83 days with placebo (P = NS). In seropositive patients, 52-week mean SELENA-SLEDAI scores were decreased by 28.8% with belimumab versus 14.2% with placebo (P < 0.05), and physician's global assessment scores were improved by 32.7% with belimumab versus 10.7% with placebo (P < 0.05). Two Phase III studies were performed in seropositive SLE patients. In a Phase III, 52-week study, the rates of response (a reduction of ≥4 points on the SLE Response Index [SRI]) at week 52 were 51% and 58% with belimumab 1 and 10 mg/kg/dose, respectively, versus 44% with placebo (both, P < 0.05). In a Phase III, 76-week study, the rates of response, as measured using SRI, at week 52 were 42.8% and 46.5% with belimumab 1 and 10 mg/kg/dose versus 35.3% with placebo (P = NS and P < 0.001); at 76 weeks, response rates were 42.1% and 41.4% with belimumab 1 and 10 mg/kg/dose versus 33.8% with placebo (P < 0.05 and P = NS). The tolerability data from these studies did not suggest any overall differences between belimumab and placebo.
Based on the findings from the present review, belimumab appears to be efficacious and generally well-tolerated and in the treatment of SLE other than lupus nephritis or neuropsychiatric lupus. Additional clinical and economics studies are needed to determine the most appropriate place for belimumab in the treatment of SLE.
贝利木单抗是一种抑制 B 淋巴细胞刺激蛋白的单克隆抗体，是美国食品和药物管理局（FDA）批准的首个用于治疗系统性红斑狼疮（SLE）的生物制剂，也是 55 年来首个用于治疗 SLE 的药物。
本文对贝利木单抗的现有研究进行综述，并就其在 SLE 治疗中的应用提供建议。
检索 Cochrane 图书馆、EBSCO、IPA、MEDLINE 和 SCOPUS 从 2000 年 1 月至 2011 年 11 月发表的研究，使用的检索词包括贝利木单抗、Benlysta 和 Lympho-Stat B。选择标准包括对贝利木单抗在 SLE 治疗中的药理学、药代动力学特性、药物相互作用以及临床疗效和耐受性的同行评审原始研究文章。还从各大风湿病医学组织和协会的年度会议摘要中搜索和审查新内容。从制造商、FDA 和其他来源获取有关贝利木单抗的其他信息。还使用 MEDLINE 选择关于 SLE 治疗的临床研究和治疗指南。
文献检索确定了 2 项 II 期和 2 项 III 期研究，这些研究比较了贝利木单抗（1、4 和 10 mg/kg/剂量 IV，分别在第 0、14 和 28 天，然后每 28 天一次）与安慰剂在接受联合治疗的活动期 SLE 患者中的疗效。患有狼疮性肾炎或神经精神性狼疮的患者被排除在外。在一项为期 52 周的 II 期研究中，24 周时，与安慰剂组（17.2%）相比，贝利木单抗组的安全性评估激素在红斑狼疮中的应用-系统性红斑狼疮疾病活动指数（SELENA-SLEDAI）评分降低了 19.5%（P=NS）。首次发作的中位时间为贝利木单抗组 67 天，安慰剂组 83 天（P=NS）。在血清阳性患者中，与安慰剂组（14.2%）相比，贝利木单抗组的 52 周平均 SELENA-SLEDAI 评分降低了 28.8%（P<0.05），医生的整体评估评分提高了 32.7%（P<0.05）。进行了两项 III 期研究以评估血清阳性 SLE 患者的疗效。在一项为期 52 周的 III 期研究中，与安慰剂组（44%）相比，贝利木单抗 1 和 10 mg/kg/剂量组在第 52 周时的缓解率（SRI 降低≥4 分）分别为 51%和 58%（均 P<0.05）。在一项为期 76 周的 III 期研究中，使用 SRI 测量的缓解率，贝利木单抗 1 和 10 mg/kg/剂量组在第 52 周时分别为 42.8%和 46.5%，安慰剂组为 35.3%（P=NS 和 P<0.001）；76 周时，缓解率分别为贝利木单抗 1 和 10 mg/kg/剂量组 42.1%和 41.4%，安慰剂组为 33.8%（P<0.05 和 P=NS）。这些研究的耐受性数据并未提示贝利木单抗与安慰剂之间存在任何总体差异。
根据本综述的研究结果，贝利木单抗似乎具有疗效，且通常具有良好的耐受性，可用于治疗除狼疮性肾炎和神经精神性狼疮以外的 SLE。需要进一步的临床和经济学研究来确定贝利木单抗在 SLE 治疗中的最佳应用位置。
