Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
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DOI：
10.1016/s0140-6736(08)60453-5
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发表时间：
2008-03-22
期刊：
影响因子：
168.9
通讯作者：
Alten, Rieke
中科院分区：
文献类型：
--
作者：
Smolen, Josef S.;Beaulieu, Andre;Alten, Rieke
背景白细胞介素6通过其对免疫和炎症反应的广泛影响参与类风湿关节炎的发病机制。我们的目的是评估通过抑制白细胞介素-6受体与托珠单抗阻断白细胞介素-6在类风湿关节炎患者中的治疗效果。方法在这项双盲、随机、安慰剂对照、平行组III期研究中，623例中重度活动性类风湿关节炎患者随机分配交互式语音应答系统，根据研究申办者提供的随机化列表按研究中心分层，接受托珠单抗8 mg/kg（n=205）、托珠单抗4 mg/kg（214）或安慰剂（204）静脉给药，每4周一次，并以稳定的研究前剂量（10-25 mg/周）给予甲氨蝶呤。在第16周，向肿胀和压痛关节计数改善均小于20%的患者提供托珠单抗8 mg/kg的补救治疗。主要终点是第24周时根据美国风湿病学会标准（ACR 20应答），类风湿性关节炎体征和症状改善20%的患者比例。该试验注册于ClinicalTrials.gov，编号NCT 00106548。结果意向治疗分析人群由622名患者组成：4 mg/kg组中的1名患者未接受研究治疗，因此被排除。在24周时，接受托珠单抗治疗的患者比接受安慰剂治疗的患者有更多的ACR 20应答（8 mg/kg组120例[59%]患者，4 mg/kg组102例[48%]患者，安慰剂组54例[26%]患者;比值比4.0 [95%CI 2.6-6.1]，p
Background Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis.Methods In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methortrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548.Findings The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p