Thymosin α1-Based Immunomodulatory Therapy for Sepsis: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials

Abstract

Background: Preclinical studies suggest that thymosin α1 has immunoregulatory and anti-inflammatory properties in various septic models. However, whether these effects will transform into improved outcomes in humans with sepsis remains unclear. We performed a meta-analysis to define the role of thymosin α1-based immunomodulatory therapy in sepsis.Methods: We searched Medline and Embase to identify randomized controlled trials that assessed the effect of thymosin α1-based immunomodulatory therapy compared with standard care for adults with sepsis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) using a random-effects model. The primary outcome was 28-day mortality.Results: Nine articles with 10 trials involving 1425 patients were included. Compared with standard care, thymosin α1-based immunomodulatory therapy was associated with a significant 31% relative risk reduction of 28-day mortality (RR 0.69, 95% CI 0.60-0.80, P<0.001), with no statistical heterogeneity (I2=0%). The benefit was confirmed by trial sequential analysis and was consistent across all subgroup analyses. For secondary outcomes, thymosin α1-based immunomodulatory therapy was associated with shorter length of intensive care unit (ICU) stay and duration of mechanical ventilation, increased T lymphocyte subsets (CD3+, CD4+, and CD4+/CD8+), and decreased inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and interleukin-6).Conclusions: Thymosin α1-based immunomodulatory therapy decreases 28-day mortality in patients with sepsis. The benefit might be attributed to its immunomodulatory and anti-inflammatory effects. However, caution should be used to translate these findings to clinical practice, because current evidence is potentially subject to bias. Hence, high-quality and adequately powered trials are still warranted.  Citation: Wan-Jie Gu, Xiao-Ping Gu, Zheng-Liang Ma. Thymosin α1-based immunomodulatory therapy for sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. J Anesth Perioper Med 2017; x: x-x. doi:10.24015/JAPM.2017.0017This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.