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

The safety, tolerability, and pharmacokinetic profile of murine monocl onal antibody to human tumor necrosis factor-alpha (TNFalpha MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic p atients. TNFalpha MAb was well tolerated in all patients, with no imme diate or delayed signs of allergic reaction. During the 28-day evaluat ion, side effects included thrombocytosis (11), hepatic enzyme elevati ons (8), cardiac arrhythmias (3), and deaths (5). Each was attributed to the patient's severe underlying disease and not to TNFalpha MAb; ho wever, a relationship between TNFalpha MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNFalpha MA b. Human antibody against TNFalpha MAb was observed in 13 (76.5%) of 1 7 phase IA patients and 10 of 10 phase IB patients and anti-idiotype a ntibodies in 11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 pha se IB patients. TNFalpha MAb should be evaluated as adjunctive therapy for patients with sepsis.