Anti-tumor necrosis factor therapy in sepsis: Update on clinical trials and lessons learned
Anti-tumor necrosis factor therapy in sepsis: Update on clinical trials and lessons learned
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DOI：
10.1097/00003246-200107001-00037
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发表时间：
2001-07-01
影响因子：
8.8
通讯作者：
Karzai, W
中科院分区：
文献类型：
--
作者：
Reinhart, K;Karzai, W
目标：肿瘤坏死因子（tumor necrosis factor，TNF）是参与脓毒症发病机制的重要介质，我们回顾了抗TNF治疗降低脓毒症患者死亡率的临床研究。数据来源：我们对研究抗TNF治疗脓毒症效果的随机、临床、多中心试验进行了计算机文献检索，我们纳入了所有的原始研究，回顾了所有发表的荟萃分析，并联系多中心试验的主要研究者在necessary.Data Synthesis，几乎所有的随机研究针对TNF在脓毒症显示一个小的，虽然不显着，在降低死亡率的好处，策略使用单克隆抗体是更有效的比策略使用TNF受体蛋白。随机多中心试验分析显示，抗TNF治疗策略的获益虽小，但意义重大。此外，最近在2634名脓毒症患者中进行的一项使用鼠抗TNF抗体的研究显示，在降低死亡率方面有3.6%的显著获益。抗TNF策略在脓毒症患者中仅部分有效，尽管个别研究显示小的、不显著的益处，对所有试验数据的分析以及最近在大量脓毒症患者中进行的试验的数据表明，抗TNF策略可能带来较小的生存益处。更好的患者特征和更多模式的方法，同时针对其他介质参与脓毒症可能有助于扩大抗TNF治疗的临床受益。
Objective: Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis, We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients.Data Sources: We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis, We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary.Data Synthesis, Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality, Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small hut significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality.Conclusions: Anti-TNF strategies are only partially effective in patients with sepsis, Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.