Clinical Safety, Tolerability, and Pharmacokinetics of Murine Monoclonal Antibody to Human Tumor Necrosis Factor-α

The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-α (TNFα MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNFα MAb was well tolerated in all patients, with no immediate or delayed signs of allerg...

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Bibliographic Details
Published in:The Journal of infectious diseases 1994-01, Vol.169 (1), p.214-217
Main Authors: Saravolatz, Louis D., Wherry, Janice C., Spooner, Christopher, Markowitz, Norman, Allred, Randy, Remick, Dan, Fournel, Michael, Pennington, James E.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - metabolism
Antibodies, Monoclonal - therapeutic use
Chemotherapy
Concise Communications
Cytokines
Dosage
Dose-Response Relationship, Drug
Dysrhythmias
Female
Follow-Up Studies
Half lives
Half-Life
Humans
Immunoglobulin G - administration & dosage
Immunoglobulin G - adverse effects
Immunoglobulin G - metabolism
Immunoglobulin G - therapeutic use
Infusions, Intravenous
Interleukin-1 - blood
Male
Metabolic Clearance Rate
Mice
Middle Aged
Monoclonal antibodies
Pharmacokinetics
Sepsis
Septic shock
Shock, Septic - blood
Shock, Septic - drug therapy
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - immunology
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Summary:The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-α (TNFα MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNFα MAb was well tolerated in all patients, with no immediate or delayed signs of allergic reaction. During the 28-day evaluation, side effects included thrombocytosis (11), hepatic enzyme elevations (8), cardiac arrhythmias (3), and deaths (5). Each was attributed to the patient's severe underlying disease and not to TNFα MAb; however, a relationship between TNFα MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNFα MAb. Human antibody against TNFα MAb was observed in 13 (76.5%) of 17 phase 1A patients and 10 of 10 phase IB patients and anti-idiotype antibodies in 11 (91.7%) of 12 phase 1A patients and 2 (33.3%) of 6 phase IB patients. TNFα MAb should be evaluated as adjunctive therapy for patients with sepsis.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/169.1.214