Rovin B H, Dooley M A, Radhakrishnan J, Ginzler E M, Forrester T D, Anderson P W
Department of Internal Medicine at their respective institutions, Ohio State University, Columbus, USA
Department of Internal Medicine at their respective institutions, University of North Carolina, Chapel Hill, USA.
Lupus. 2016 Dec;25(14):1597-1601. doi: 10.1177/0961203316650734. Epub 2016 May 24.
Tabalumab is a monoclonal antibody that neutralizes membrane and soluble B-cell activating factor. Two 52-week, randomized, double-blind, placebo controlled phase 3 trials evaluated the safety and efficacy of tabalumab in systemic lupus erythematosus.
Patients with moderate to severe active systemic lupus erythematosus (without severe active lupus nephritis) were randomly assigned 1:1:1 to receive tabalumab (120 mg subcutaneously every 2 or 4 weeks) or placebo for 52 weeks. Serum creatinine concentration, estimated glomerular filtration rate, urine protein/creatinine ratio, renal flares and renal adverse events were determined monthly. Data were analyzed for the intent-to-treat population and for intent-to-treat patients with baseline urine protein/creatinine ratio >20 mg/mmol (intent-to-treat plus urine protein/creatinine ratio).
The trials enrolled 2262 patients. At baseline, demographics, systemic lupus erythematosus disease activity, serum creatinine concentration, estimated glomerular filtration rate and urine protein/creatinine ratio were similar among the treatment arms (with the exception of disease duration). In the intent-to-treat and intent-to-treat plus urine protein/creatinine ratio populations, there were no differences between the arms in the baseline-to-endpoint change in serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates. Tabalumab resulted in a significant B-cell reduction and decreased immunoglobulin G levels at both doses.
Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.
他巴鲁单抗是一种可中和膜结合型及可溶性B细胞活化因子的单克隆抗体。两项为期52周的随机、双盲、安慰剂对照3期试验评估了他巴鲁单抗治疗系统性红斑狼疮的安全性和疗效。
将中度至重度活动性系统性红斑狼疮（无严重活动性狼疮性肾炎）患者按1:1:1随机分组，接受他巴鲁单抗（每2或4周皮下注射120mg）或安慰剂治疗52周。每月测定血清肌酐浓度、估算肾小球滤过率、尿蛋白/肌酐比值、肾脏活动度及肾脏不良事件。对意向性治疗人群以及基线尿蛋白/肌酐比值>20mg/mmol的意向性治疗患者（意向性治疗加尿蛋白/肌酐比值）进行数据分析。
试验共纳入2262例患者。基线时，各治疗组的人口统计学特征、系统性红斑狼疮疾病活动度、血清肌酐浓度、估算肾小球滤过率及尿蛋白/肌酐比值相似（疾病持续时间除外）。在意向性治疗人群以及意向性治疗加尿蛋白/肌酐比值人群中，各治疗组间血清肌酐浓度、肾小球滤过率、尿蛋白/肌酐比值或肾脏活动度从基线到终点的变化无差异。两种剂量的他巴鲁单抗均导致B细胞显著减少及免疫球蛋白G水平降低。
与安慰剂相比，在接受意向性治疗或意向性治疗加尿蛋白/肌酐比值的患者中，他巴鲁单抗在1年内未显著影响血清肌酐浓度、肾小球滤过率、尿蛋白/肌酐比值或肾脏活动度。未发现显著的肾脏安全信号。ClinicalTrials.gov标识符：NCT01205438和NCT01196091 狼疮（2016年）25卷，1597 - 1601页
