Emerging therapies for immunomodulation in traumatic brain injury: A systematic review and meta-analysis

Traumatic brain injury (TBI) represents a significant global health burden, often leading to significant morbidity and mortality. Mounting evidence underscores the intricate involvement of dysregulated immune responses in TBI pathophysiology, highlighting the potential for immunomodulatory interventions to mitigate secondary injury cascades and enhance patient outcomes. Despite advancements in treatment modalities, optimizing therapeutic strategies remains a critical challenge in TBI management. To address this gap, this systematic review and meta-analysis aimed to rigorously evaluate the efficacy and safety of emerging immunomodulatory therapies in the context of TBI. We searched electronic databases such as PubMed, Scopus, Web of Science and CENTRAL for relevant studies investigating the efficacy of immunomodulatory therapies in TBI that were meticulously selected for inclusion. Two independent reviewers meticulously performed data extraction and quality assessment, adhering to predefined criteria. Both randomized controlled trials (RCTs) and observational studies reporting clinically relevant outcomes, such as mortality rates, the Glasgow coma scale, and adverse events, were meticulously scrutinized. Meta-analysis techniques were employed to assess treatment effects across studies quantitatively and analyzed using the Review Manager software (version 5.2). Fourteen studies ( = 1 observational and = 13 RCTs) were included in our study. Meta-analysis showed no significant overall mortality difference, but erythropoietin (EPO) significantly reduced mortality (odds ratio = 0.49; 95% confidence interval: 0.31-0.78, = 0.002). The adverse event meta-analysis revealed no significant differences. Immunomodulatory therapies did not significantly affect overall mortality, but EPO demonstrated promising results. Adverse events did not significantly differ from controls. Further research is warranted to refine TBI treatment protocols.