Meng Xianmin, Wang Qianqian, Wu Shunquan, Pu Di, Zhang Amber, Fang Sun, Zhou Xuan, Lu Hongzhou
Department of Pharmacy, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Department of Internal Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Rheumatol Ther. 2021 Dec;8(4):1711-1724. doi: 10.1007/s40744-021-00366-0. Epub 2021 Sep 23.
Belimumab is a recombinant human immunoglobulin G1λ monoclonal antibody indicated as an intravenous (IV) 10 mg/kg and subcutaneous (SC) 200-mg dose for the treatment of systemic lupus erythematosus (SLE). Belimumab 10 mg/kg IV has been approved for the treatment of patients with SLE in China. This phase 1 study investigated the pharmacokinetics (PK), safety, and tolerability of belimumab 200 mg SC and the approved IV formulation in a healthy Chinese population.
This was a 13-week open-label, randomized, parallel-group study in healthy Chinese volunteers. Eligible volunteers were randomized (1:2) to receive a single dose of IV or SC (via auto-injector) belimumab 200 mg. PK and safety endpoints were evaluated using descriptive statistics.
Thirty-six healthy Chinese volunteers were enrolled and all completed the study. Concentration-time profiles were as expected for both formulations. Overall, 130 adverse events (AEs) were reported, with 28 AEs reported in 11 (91.7%) volunteers in the IV group and 102 AEs in 24 (100%) volunteers in the SC group. Of the 130 AEs, 104 (80.0%) were considered to be treatment-related (27 [20.8% of total AEs] treatment-related AEs in the IV group; 77 [59.2% of total AEs] in the SC group). Although the occurrence of AEs was higher in the SC group, most volunteers (91.7%) experienced AEs of mild intensity. The most frequently reported AEs included injection site pain (n = 19 [79.2%]) and oropharyngeal pain (n = 5 [20.8%]) in the SC group, and positive bacterial test, upper respiratory tract infection, blood uric acid increase, white blood cell count increase, asthenia, and diarrhea (n = 2 [16.7%], each) in the IV group.
PK profiles of 200 mg SC and IV belimumab administrations were similar to previous studies, and safety profiles were acceptable, supporting the use of the SC dose in Chinese patients with SLE.
NCT04136145.
贝利尤单抗是一种重组人免疫球蛋白G1λ单克隆抗体，静脉注射剂量为10mg/kg，皮下注射剂量为200mg，用于治疗系统性红斑狼疮（SLE）。贝利尤单抗10mg/kg静脉注射已在中国获批用于治疗SLE患者。这项1期研究在健康中国人群中调查了200mg皮下注射贝利尤单抗和已获批的静脉注射制剂的药代动力学（PK）、安全性和耐受性。
这是一项针对健康中国志愿者的为期13周的开放标签、随机、平行组研究。符合条件的志愿者被随机分组（1:2），接受单剂量200mg静脉注射或皮下注射（通过自动注射器）贝利尤单抗。使用描述性统计评估PK和安全性终点。
招募了36名健康中国志愿者，所有志愿者均完成了研究。两种制剂的浓度-时间曲线均符合预期。总体而言，共报告了130例不良事件（AE），静脉注射组11名（91.7%）志愿者报告了28例AE，皮下注射组24名（100%）志愿者报告了102例AE。在这130例AE中，104例（80.0%）被认为与治疗相关（静脉注射组27例[占总AE的20.8%]与治疗相关的AE；皮下注射组77例[占总AE的59.2%]）。虽然皮下注射组AE的发生率较高，但大多数志愿者（91.7%）经历的是轻度AE。皮下注射组最常报告的AE包括注射部位疼痛（n = 19[79.2%]）和口咽痛（n = 5[20.8%]），静脉注射组最常报告的AE包括细菌检测阳性、上呼吸道感染、血尿酸升高、白细胞计数升高、乏力和腹泻（各n = 2[16.7%]）。
200mg皮下注射和静脉注射贝利尤单抗的PK曲线与先前研究相似，安全性概况可接受，支持在中国SLE患者中使用皮下注射剂量。
NCT04136145。
