Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials
Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials
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DOI：
10.1136/ard.2008.094904
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发表时间：
2009-07-01
影响因子：
27.4
通讯作者：
Sutton, A. J.
中科院分区：
文献类型：
--
作者：
Bongartz, T.;Warren, F. C.;Sutton, A. J.
目的：肿瘤坏死因子（TNF）在炎症中起重要作用，并可能影响肿瘤生长控制。为了评估恶性肿瘤的风险与依那西普，融合蛋白，抑制肿瘤坏死因子的行动，荟萃分析进行了使用随机对照试验（RCT）在类风湿性关节炎（RA）患者的个体患者的数据：方法：进行检索的书目数据库，摘要从年度会议和任何未发表的研究文件与依那西普制造商到2006年12月。仅纳入依那西普在RA患者中使用12周或更长时间的RCT。9项试验符合纳入标准。为了裁定终点，审查了潜在病例的病例叙述。从临床试验databases.Results中提取患者水平的数据：9项试验包括3316例患者，2244人接受依那西普（贡献2484人-年的后续行动）和1072人接受对照治疗（1051人-年）。依那西普组有26例患者（发病率（IR）为10.47/1000人-年）和对照组有7例患者（IR为6.66/1000人-年）被诊断为恶性肿瘤。一个考克斯的比例风险，固定效应模型分层试验产生的风险比为1.84（95%CI 0.79至4.28）为依那西普组与对照group.Conclusions相比：在这项分析中，恶性肿瘤风险的点估计是较高的依那西普治疗的患者，虽然结果没有统计学意义。与试验申办者合作获得RCT个体患者数据的方法使我们能够深入了解稀疏不良事件数据荟萃分析的方法学优势和挑战。
Purpose: Tumour necrosis factor (TNF) plays an important role in inflammation and may affect tumour growth control. To assess the risk of malignancy with etanercept, a fusion protein that inhibits TNF action, a meta-analysis was performed using individual patient data from randomised controlled trials (RCT) in patients with rheumatoid arthritis (RA).Methods: A search was conducted of bibliographic databases, abstracts from annual meetings and any unpublished studies on file with manufacturers of etanercept to December 2006. Only RCT of etanercept used for 12 weeks or more in patients with RA were included. Nine trials met the inclusion criteria. To adjudicate endpoints, the case narratives of potential cases were reviewed. Patient-level data were extracted from the clinical trials databases.Results: The nine trials included 3316 patients, 2244 who received etanercept (contributing 2484 person-years of follow-up) and 1072 who received control therapy (1051 person-years). Malignancies were diagnosed in 26 patients in the etanercept group (incidence rate (IR) 10.47/1000 person-years) and seven patients in the control group (IR 6.66/1000 person-years). A Cox's proportional hazards, fixed-effect model stratified by trial yielded a hazard ratio of 1.84 (95% CI 0.79 to 4.28) for the etanercept group compared with the control group.Conclusions: In this analysis, the point estimate of malignancy risk was higher in etanercept-treated patients, although the results were not statistically significant. The approach of obtaining individual patient data of RCT in cooperation with trial sponsors allowed important insights into the methodological advantages and challenges of sparse adverse event data meta-analysis.