Bongartz T, Warren F C, Mines D, Matteson E L, Abrams K R, Sutton A J
Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Ann Rheum Dis. 2009 Jul;68(7):1177-83. doi: 10.1136/ard.2008.094904. Epub 2008 Nov 19.
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).
A search was conducted of bibliographic databases, abstracts from annual meetings and any unpublished studies on file with manufacturers of etanercept to December 2006.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.
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.
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.
肿瘤坏死因子（TNF）在炎症中起重要作用，可能影响肿瘤生长控制。为评估肿瘤坏死因子拮抗剂（一种抑制TNF作用的融合蛋白）治疗导致恶性肿瘤的风险，我们使用类风湿关节炎（RA）患者随机对照试验（RCT）的个体患者数据进行了一项荟萃分析。
检索了文献数据库、年会摘要以及截至2006年12月肿瘤坏死因子拮抗剂制造商存档的所有未发表研究。仅纳入了在RA患者中使用肿瘤坏死因子拮抗剂12周或更长时间的RCT。9项试验符合纳入标准。为判定终点，对潜在病例的病例记录进行了审查。从临床试验数据库中提取了患者水平的数据。
9项试验共纳入3316例患者，其中2244例接受肿瘤坏死因子拮抗剂治疗（随访人年数为2484人年），1072例接受对照治疗（1051人年）。肿瘤坏死因子拮抗剂组有26例患者被诊断为恶性肿瘤（发病率10.47/1000人年），对照组有7例患者（发病率6.66/1000人年）。采用Cox比例风险固定效应模型，按试验分层，肿瘤坏死因子拮抗剂组与对照组相比，风险比为1.84（95%CI 0.79至4.28）。
在本分析中，接受肿瘤坏死因子拮抗剂治疗的患者发生恶性肿瘤风险的点估计值较高，尽管结果无统计学意义。与试验申办者合作获取RCT个体患者数据的方法，使我们对稀疏不良事件数据荟萃分析的方法学优势和挑战有了重要认识。
