Pavelka Karel, Chon Yun, Newmark Richard, Lin Shao-Lee, Baumgartner Scott, Erondu Ngozi
From the Institute of Rheumatology, Prague, Czech Republic; and Amgen Inc., Thousand Oaks, California, USA.K. Pavelka, MD, PhD, Institute of Rheumatology; Y. Chon, PhD; R. Newmark, PhD, Amgen Inc.; S.L. Lin, MD, PhD; S. Baumgartner, MD, formerly employed by Amgen Inc.; N. Erondu, MD, PhD, Amgen Inc.
J Rheumatol. 2015 Jun;42(6):912-9. doi: 10.3899/jrheum.141271. Epub 2015 Apr 15.
To evaluate the efficacy and safety of brodalumab, a human monoclonal antibody inhibitor of the interleukin 17 receptor, in subjects with rheumatoid arthritis (RA).
Patients (n = 252) with inadequate response to methotrexate (MTX) were randomized to receive subcutaneous injections of brodalumab (70 mg, 140 mg, or 210 mg) or placebo. The primary endpoint was the American College of Rheumatology 50% response (ACR50) at Week 12.
Demographics and baseline characteristics were generally balanced among treatment groups. At Week 12, ACR50 occurred in 16% (70 mg), 16% (140 mg), 10% (210 mg), and 13% (placebo; all nonsignificant vs placebo) of subjects. No significant treatment effects were observed for the secondary endpoints, including ACR20, ACR70, and Disease Activity Score in 28 joints. Incidences of all adverse events (AE), including serious AE (SAE), were similar across treatment groups. A total of 7 subjects reported SAE during the study (2 in the placebo group and 5 in the brodalumab groups), none of which was treatment related. There was 1 death (cardiopulmonary failure) ∼1 week after the last dose in the 140 mg group.
Our study failed to find evidence of meaningful clinical efficacy with brodalumab treatment in subjects with RA who had an inadequate response to MTX. These preliminary results do not support further evaluation of brodalumab as a treatment for RA. Clinicaltrials.gov number: NCT00950989.
评估人白细胞介素17受体单克隆抗体抑制剂布罗达单抗治疗类风湿关节炎（RA）患者的疗效和安全性。
对甲氨蝶呤（MTX）治疗反应不佳的患者（n = 252）被随机分为皮下注射布罗达单抗（70 mg、140 mg或210 mg）或安慰剂组。主要终点为第12周时美国风湿病学会50%反应率（ACR50）。
各治疗组的人口统计学和基线特征总体平衡。在第12周时，接受70 mg（16%）、140 mg（16%）、210 mg（10%）布罗达单抗治疗的患者以及接受安慰剂治疗的患者（13%）中达到ACR50，与安慰剂组相比差异均无统计学意义。次要终点包括ACR20、ACR70和28个关节疾病活动评分，均未观察到显著的治疗效果。各治疗组所有不良事件（AE）的发生率，包括严重不良事件（SAE），均相似。研究期间共有7名受试者报告了SAE（安慰剂组2例，布罗达单抗组5例），均与治疗无关。140 mg组在最后一剂药物后约1周有1例死亡（心肺衰竭）。
在对MTX反应不佳的RA患者中，我们的研究未发现布罗达单抗治疗具有有意义的临床疗效的证据。这些初步结果不支持进一步评估布罗达单抗用于RA的治疗。临床试验注册号：NCT00950989。
