Lv S, Han M, Yi R, Kwon S, Dai C, Wang R
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan Shandong, China.
Int J Clin Pract. 2014 Apr;68(4):520-8. doi: 10.1111/ijcp.12382. Epub 2014 Feb 18.
In humans, the role of anti-tumour necrosis factor (TNF)-α therapy in severe sepsis and septic shock is debatable. The aim of this meta-analysis was to determine the efficacy of anti-TNF-α therapies against placebo in patients with severe sepsis or septic shock.
A structured literature search was undertaken to identify randomised controlled trials (RCTs) conducted in patients with severe sepsis or septic shock receiving anti-TNF-α therapy or placebo. A meta-analysis on relative risk (OR) with a 95% confidence interval (95% CI) was performed.
Seventeen studies with a total of 8971 patients were included. When all forms of anti-TNF-α therapy were pooled together, there was a significant reduction of 28-day all-cause mortality with respect to placebo (OR = 0.91, 95% CI: 0.83-0.99; p = 0.04). Subgroup analysis showed that anti-TNF-α antibodies (monoclonal and polyclonal) reduced mortality (OR = 0.90, 95% CI: 0.81-0.99; p = 0.04). Monoclonal antibodies enhanced survival (OR = 0.91, 95% CI: 0.82-1.00; p = 0.05), while polyclonal antibodies or receptor blockers did not enhance survival (OR = 0.71, 95% CI: 0.39-1.28, p = 0.25; OR = 0.95, 95% CI: 0.78-1.17, p = 0.65). There was a trend towards better survival in patients with high levels of IL-6 (> 1000 pg/ml) and patients with shock if they were treated with anti-TNF-α therapy (OR = 0.85, 95% CI: 0.72-1.00; OR = 0.80, 95% CI: 0.62-1.04). Publication bias and statistical heterogeneity (I(2) < 50% and p > 0.1) were absent. Sensitivity analysis suggests that these results are highly stable.
This meta-analysis suggests that in patients with severe sepsis (before shock), immunotherapy with anti-TNF-α monoclonal antibodies reduces overall mortality. In patients with shock or high levels of IL-6 (> 1000 pg/ml), anti-TNF-α therapy may improve survival.
在人类中，抗肿瘤坏死因子（TNF）-α疗法在严重脓毒症和脓毒性休克中的作用存在争议。本荟萃分析的目的是确定抗TNF-α疗法对比安慰剂治疗严重脓毒症或脓毒性休克患者的疗效。
进行结构化文献检索，以识别在接受抗TNF-α疗法或安慰剂治疗的严重脓毒症或脓毒性休克患者中开展的随机对照试验（RCT）。对相对风险（OR）及95%置信区间（95%CI）进行荟萃分析。
纳入17项研究，共8971例患者。当将所有形式的抗TNF-α疗法合并在一起时，与安慰剂相比，28天全因死亡率显著降低（OR = 0.91，95%CI：0.83 - 0.99；p = 0.04）。亚组分析显示，抗TNF-α抗体（单克隆和多克隆）降低了死亡率（OR = 0.90，95%CI：0.81 - 0.99；p = 0.04）。单克隆抗体提高了生存率（OR = 0.91，95%CI：0.82 - 1.00；p = 0.05），而多克隆抗体或受体阻滞剂未提高生存率（OR = 0.71，95%CI：0.39 - 1.28，p = 0.25；OR = 0.95，95%CI：0.78 - 1.17，p = 0.65）。对于白细胞介素-6水平高（> 1000 pg/ml）的患者和休克患者，如果接受抗TNF-α疗法，有生存改善的趋势（OR = 0.85，95%CI：0.72 - 1.00；OR = 0.80，95%CI：0.62 - 1.04）。不存在发表偏倚和统计学异质性（I(2) < 50%且p > 0.1）。敏感性分析表明这些结果高度稳定。
本荟萃分析表明，在严重脓毒症（休克前）患者中，抗TNF-α单克隆抗体免疫疗法可降低总体死亡率。在休克患者或白细胞介素-6水平高（> 1000 pg/ml）的患者中，抗TNF-α疗法可能改善生存率。
