CLINICAL SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MURINE MONOCLONAL-ANTIBODY TO HUMAN TUMOR-NECROSIS-FACTOR-ALPHA

The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-alpha (TNFalpha MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNFalpha 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 TNFalpha MAb; however, a relationship between TNFalpha MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNFalpha MAb. Human antibody against TNFalpha MAb was observed in 13 (76.5%) of 17 phase IA patients and 10 of 10 phase IB patients and anti-idiotype antibodies in 11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 phase IB patients. TNFalpha MAb should be evaluated as adjunctive therapy for patients with sepsis.