Anti-TNF-α therapy for patients with sepsis: a systematic meta-analysis

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.