Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis.
Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials: a meta-analysis.
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DOI：
10.1097/ccm.0b013e3182982add
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发表时间：
2013-10
影响因子：
8.8
通讯作者：
Eichacker PQ
中科院分区：
文献类型：
--
作者：
Qiu P;Cui X;Sun J;Welsh J;Natanson C;Eichacker PQ
Sepsis is a lethal syndrome annually affecting ~900,000 patients in the United States alone. Despite their benefit in rheumatoid disease, selective anti-tumor necrosis factor (anti-TNF) agents failed to improve outcome in early sepsis trials in the 1990’s. However, data from additional sepsis trials testing these agents is now available. To determine the effect on survival of selective anti-TNF agents in randomized clinical sepsis trials. PubMed, Scopus, EMBASE, and Web of Science. Randomized human sepsis trials of selective anti-TNF agents reporting survival rates. Two investigators independently collected relevant data on study characteristics, treatment interventions, and patient from each study. Anti-TNF agents in 15 sepsis trials (n=8,896 patients) meeting inclusion criteria had similar effects (I2=0, p=0.84) and compared to controls (placebo in 14 trials or a lower dose in 1 trial) overall decreased the relative risk (RR) of death (95% CI) [0.93 (0.88, 0.98), p=0.01]. In subgroup analysis, TNF monoclonal antibodies (10 trials, n=6,818) alone produced a significant survival benefit [0.93 (0.87, 0.99), p=0.02] (I2=0, p=0.83). TNF polyclonal antibodies (2 trials, n=151) and low molecular weight soluble receptor (2 trials, n=1,786) had similar beneficial effects to anti-TNF agents overall [0.82(0.49, 1.37), p=0.45; 0.93(0.81, 1.08), p=0.33, respectively]. The effect of TNF high molecular weight soluble receptor (1 trial, n=141) was not significantly different from other agents but was on the side of harm [1.50 (0.86, 2.61), p=0.16]. Limited secondary end-point data. Anti-TNF agents produced a modest but significant decrease in the risk of dying with sepsis. Prior individual trials failed to demonstrate benefit, likely because they were underpowered. A definitive trial demonstrating the potential benefit of such agents might require 10,000 or more septic patients.
