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托珠单抗与其他生物制剂治疗对改善病情抗风湿药反应不佳的类风湿关节炎患者的间接比较。

Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.

机构信息

Mapi Values, Houten, The Netherlands.

出版信息

Semin Arthritis Rheum. 2010 Jun;39(6):425-41. doi: 10.1016/j.semarthrit.2009.12.002. Epub 2010 Mar 11.

Abstract

OBJECTIVES

To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR).

METHODS

Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (<ACR20, ACR20-50, ACR50-70, >ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI).

RESULTS

Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1).

CONCLUSIONS

Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.

摘要

目的

比较托珠单抗与其他生物制剂在改善病情抗风湿药物(DMARD)反应不足的类风湿关节炎患者中的美国风湿病学会(ACR)反应模式。

方法

系统文献检索确定了 18 年来设计相似的双盲、随机、安慰剂对照试验,研究了阿巴西普(2)、利妥昔单抗(2)和 TNF-α抑制剂依那西普、英夫利昔单抗和阿达木单抗(11)在 DMARD 反应不足患者中的疗效;纳入了三种新开发的 IL-6 抑制剂托珠单抗的 3 项安慰剂对照、3 期临床试验的数据。感兴趣的终点是 24 至 30 周时 ACR20/50/70 反应标准。使用贝叶斯混合治疗比较技术同时分析结果。比较每种药物的非重叠 ACR 反应率(<ACR20、ACR20-50、ACR50-70、>ACR70),以确定 ACR 反应模式的差异。对重叠的 ACR20/50/70 反应进行单独分析,以确定任何差异的来源。结果表示为 ACR20/50/70 反应的相对风险及其相关 95%可信区间(CrI)。

结果

非重叠 ACR 反应水平的模式在治疗之间差异显著。在随后的分析中,托珠单抗在 ACR20 和 ACR50 反应方面的疗效似乎与其他生物制剂相当,但在 ACR70 方面的疗效更高。具体而言,托珠单抗的 ACR70 反应大于 TNF-α抑制剂(相对风险=1.8;CrI=1.2,2.6)和阿巴西普(相对风险=2.0;CrI=1.3,3.1)。

结论

在 DMARD 反应不足的患者中,托珠单抗表现出与其他生物制剂不同的反应模式。事后分析表明,差异在于托珠单抗更有可能实现 ACR70 反应。

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