Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab′)2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels*
| Autor: | Lothar Daum, Mark A. Miller, Gregory Hicklin, John C. Marshall, Christopher J. Doig, Edward A. Panacek, Leah Teoh, William T. Barchuk, Lori Van Meter, Martin Kaul, Rodger D. MacArthur, Timothy E Albertson, David H. Johnson, Steven Fischkoff, Stanley Lemeshow, Steven B. Johnson |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Canada medicine.medical_specialty Critical Care Multiple Organ Failure Population Critical Care and Intensive Care Medicine Placebo Gastroenterology Sepsis Double-Blind Method Risk Factors Cause of Death Intensive care Internal medicine medicine Humans Prospective Studies Infusions Intravenous education APACHE Proportional Hazards Models education.field_of_study Interleukin-6 business.industry Mortality rate Organ dysfunction Antibodies Monoclonal Middle Aged medicine.disease Survival Analysis United States Surgery Logistic Models Treatment Outcome Relative risk Tumor Necrosis Factors Afelimomab Female Safety medicine.symptom business medicine.drug |
| Zdroj: | Critical Care Medicine. 32:2173-2182 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/01.ccm.0000145229.59014.6c |
| Popis: | Objective: To evaluate whether administration of afelimomab, an anti-tumor necrosis factor F(ab')2 monoclonal antibody fragment, would reduce 28-day all-cause mortality in patients with severe sepsis and elevated serum levels of IL-6. Design: Prospective, randomized, double-blind, placebo-controlled, multiple-center, phase III clinical trial. Setting: One hundred fifty-seven intensive care units in the United States and Canada. Patients: Subjects were 2,634 patients with severe sepsis secondary to documented infection, of whom 998 had elevated interleukin-6 levels. Interventions: Patients were stratified into two groups by means of a rapid qualitative interleukin-6 test kit designed to identify patients with serum interleukin-6 levels above (test positive) or below (test negative) approximately 1000 pg/mL. Of the 2,634 patients, 998 were stratified into the test-positive group, 1,636 into the test-negative group. They were then randomly assigned 1:1 to receive afelimomab 1 mg/kg or placebo for 3 days and were followed for 28 days. The a priori population for efficacy analysis was the group of patients with elevated baseline interleukin-6 levels as defined by a positive rapid interleukin-6 test result. Measurements and Main Results: In the group of patients with elevated interleukin-6 levels, the mortality rate was 243 of 510 (47.6%) in the placebo group and 213 of 488 (43.6%) in the afelimomab group. Using a logistic regression analysis, treatment with afelimomab was associated with an adjusted reduction in the risk of death of 5.8% (p .041) and a corresponding reduction of relative risk of death of 11.9%. Mortality rates for the placebo and afelimomab groups in the interleukin-6 test negative population were 234 of 819 (28.6%) and 208 of 817 (25.5%), respectively. In the overall population of interleukin-6 test positive and negative patients, the placebo and afelimomab mortality rates were 477 of 1,329 (35.9%)and 421 of 1,305 (32.2%), respectively. Afelimomab resulted in a significant reduction in tumor necrosis factor and interleukin-6 levels and a more rapid improvement in organ failure scores compared with placebo. The safety profile of afelimomab was similar to that of placebo. Conclusions: Afelimomab is safe, biologically active, and well tolerated in patients with severe sepsis, reduces 28-day all-cause mortality, and attenuates the severity of organ dysfunction in patients with elevated interleukin-6 levels. (Crit Care Med 2004; 32:2173‐2182) |
| Databáze: | OpenAIRE |
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