The addition of tocilizumab to DMARD therapy for rheumatoid arthritis: a meta-analysis of randomized controlled trials
The addition of tocilizumab to DMARD therapy for rheumatoid arthritis: a meta-analysis of randomized controlled trials
复制标题
在 DMARD 治疗类风湿性关节炎中添加托珠单抗：随机对照试验的荟萃分析
DOI：
10.1007/s00228-009-0754-0
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Jiang, Yuan Ying
中科院分区：
文献类型：
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作者：
An, Mao Mao;Zou, Zui;Jiang, Yuan Ying
Tocilizumab是一种人源化的与白细胞介素6受体结合的单抗。本研究的目的是评价在抗风湿药物(DMARD)治疗类风湿关节炎(RA)的基础上加用西利珠单抗的疗效。主要疗效结果是根据美国风湿病学会(ACR)标准(ACR20反应)，RA症状和体征改善20%的患者比例。主要的安全性结果是报告至少一个不良事件的患者比例和报告至少一个严重不良事件的患者比例。结果涉及2701名患者的4项随机对照试验进入Meta分析。在DMARDS的治疗方案中加入tocilizumab在临床和统计学上都与达到ACR20反应的患者数量增加[8 mg/kg，风险比(RR)2.53，95%可信区间(CI)1.89-3.39；4 mg/kg，RR 1.96，95%CI 1.40-2.73]，以及ACR50和ACR70反应，并根据基于28个关节的疾病活动评分显示缓解。然而，这些好处是以患者发生更多不良事件的倾向为代价的(8 mg/kg，RR 1.12，95%CI 1.03-1.20；4 mg/kg，RR 1.08，95%CI 1.00-1.17)。新的发现是，增加tocilizumab剂量(从4 mg/kg到8 mg/kg)的临床益处与较高的不良事件发生率无关。结论tocilizumab+DMARD联合治疗的疗效与患者发生更多不良事件的倾向有关。因此，在类风湿关节炎治疗中，这些联合治疗的利弊应该谨慎地相互权衡。我们建议每4周服用一次8 mg/kg的tocilizumab为推荐剂量。
PurposeTocilizumab is a humanized monoclonal antibody that binds to the interleukin-6 receptor. The purpose of this study was to evaluate the effect of adding tocilizumab to disease-modifying antirheumatic drug (DMARD) therapy for the treatment of rheumatoid arthritis (RA).MethodsWe performed a meta-analysis of relevant randomized controlled trials (RCTs) identified in PubMed, Cochrane library, and Embase. The primary efficacy outcome was the proportion of patients with a 20% improvement in RA signs and symptoms according to American College of Rheumatology (ACR) criteria (ACR20 response). The primary safety outcomes were the proportion of patients reporting at least one adverse event and the proportion of patients reporting at least one serious adverse event.ResultsFour RCTs, involving 2701 patients, were included in our meta-analysis. The addition of tocilizumab to therapeutic regimens with DMARDs was associated both clinically and statistically with an increased number of patients achieving the ACR20 response [8 mg/kg, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.89–3.39; 4 mg/kg, RR 1.96, 95% CI 1.40–2.73], as well as the ACR50 and ACR70 response, and showing remission according to the Disease Activity Score based on 28 joints. However, the benefits were gained at the expense of the tendency of the patient to experience more adverse events (8 mg/kg, RR 1.12, 95% CI 1.03–1.20; 4 mg/kg, RR 1.08, 95% CI 1.00–1.17). The new finding was that the clinical benefit from the increased tocilizumab dose (from 4 to 8 mg/kg) was not correlated with a higher incidence of adverse events.ConclusionsThe superior efficacy of combined tocilizumab + DMARD therapy is associated with the tendency for the patient to have more adverse events. Consequently, the benefits and disadvantages of such combined treatments should be carefully balanced against each other in RA therapy. We suggest that 8 mg/kg every 4 weeks should be the recommended dose of tocilizumab.