Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.
OBJECTIVE
Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis. We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients.


METHODS
We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis. We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary.


RESULTS
Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality. Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small but significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality.


CONCLUSIONS
Anti-TNF strategies are only partially effective in patients with sepsis. Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.
Reinhart
K
K
Department of Anesthesiology and Intensive Care Medicine, University Hospital, Jena, Germany. Konrad.Reinhart@med.uni-jena.de
Karzai
W
W
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use; D012107:Research Design; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C402162:CDP 571; C427683:afelimomab