Immunomodulatory Therapy and Mortality in Patients with Sepsis: A Meta-Analysis.

INTRODUCTION: Sepsis, a severe infectious disease, is characterized by high mortality and significant therapeutic challenges. This study aims to systematically review the impact of immunomodulatory therapy on sepsis-related mortality and create an evidence-based foundation for sepsis treatment. METHODS: A systematic search was conducted in multiple databases including CNKI, VIP, Wanfang Data, and PubMed, with a cutoff date of November 6, 2024. The Cochrane Risk of Bias 2.0 tool was employed to evaluate the risk of bias for randomized controlled trials (RCTs), and the Newcastle-Ottawa Scale was used for non-RCTs (NRCTs). Data analyses were conducted via the R package meta, with the relative risk (RR) and 95% CI as effect sizes. Heterogeneity was evaluated using the Cochran's Q test and I2 statistic, and publication bias was judged by a funnel plot. RESULTS: A total of 1,783 articles were retrieved, and 21 articles (including 22 comparison groups) were finally included after screening, involving 19 RCTs and 2 NRCTs with a total of 5,276 patients. Meta-analysis results indicated that immunomodulatory therapy could reduce the risk of death in patients with sepsis (RR = 0.87, 95% CI: 0.81-0.93, I2 = 44%, p = 0.01). Subgroup analysis revealed that the overall heterogeneity mainly came from immunoglobulin G therapy (I2 = 63%), while the effects of afelimomab, methylprednisolone, Xuebijing, α1-thymosin (Tα1), and ulinastatin + Tα1 therapies were highly consistent with zero heterogeneity. CONCLUSION: Immunomodulatory therapy can reduce the risk of death in patients with sepsis, but there is moderate heterogeneity, and its efficacy may be affected by factors such as the type of specific immunomodulatory therapy.