Current Status of Clinical Trials With Anti-TNF

Abstract

Sepsis continues to be a prominent problem in the United States and around the world, with up to 500,000 cases per year reported in the United States alone. 1 Wenzel R Anti-endotoxin monoclonal antibodies—a second look. N Engl J Med. 1992; 326: 1151-1153 Crossref PubMed Scopus (121) Google Scholar Mortality in sepsis ranges from 20 to 50%; in patients who develop septic shock, mortality increases to 40 to 70%. 2 Young L Sepsis syndrome. in: Mandell G Bennett J Dolan R Principles and practice of infectious diseases. 4th. Churchill Livingston, New York1995: 690-705 Google Scholar , 3 Bone R Fisher CJ Clemmer T et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987; 317: 653-658 Crossref PubMed Scopus (1077) Google Scholar , 4 The Veterans Administration Systemic Sepsis Cooperative Study GroupEffect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med. 1987; 317: 659-665 Crossref PubMed Scopus (639) Google Scholar , 5 Ispahani P Pearson N Greenwood D An analysis of community and hospital-acquired bacteraemia in a large teaching hospital in the United Kingdom. QJM. 1987; 63: 427-440 PubMed Google Scholar , 6 Ziegler E Fisher CJ Sprung C et al. Treatment of Gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomized, double-blind, placebo-controlled trial. N Engl J Med. 1991; 324: 429-436 Crossref PubMed Scopus (1280) Google Scholar , 7 Parrillo J Management of septic shock: present and future. Ann Intern Med. 1991; 115: 491-493 Crossref PubMed Scopus (43) Google Scholar , 8 Abraham E Wunderink R Silverman H et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome: a randomized, controlled, double-blind, multicenter clinical trial. JAMA. 1995; 273: 934-941 Crossref PubMed Scopus (780) Google Scholar , 9 Cohen J Carlet J INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-α in patients with sepsis. Crit Care Med. 1996; 24: 1431-1440 Crossref PubMed Scopus (430) Google Scholar , 10 Fisher Jr, CJ Dhainaut JF Opal SM et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome: results from a randomized, double-blind, placebo-controlled trial. JAMA. 1994; 271: 1836-1843 Crossref PubMed Scopus (956) Google Scholar The mortality rate has remained largely constant during the postantibiotic era. The incidence of mortality from sepsis, however, has actually increased over the last l½ decades, 11 Pinner R Teutsch S Simonsen L et al. Trends in infectious diseases mortality in the United States. JAMA. 1996; 275: 189-193 Crossref PubMed Google Scholar presumably due to an aging population, an increase in the number of invasive procedures performed, and possibly alterations in the infecting micro-organisms.