REPEATED ADMINISTRATION OF A F(AB')2 FRAGMENT OF AN ANTITUMOR NECROSIS FACTOR-ALPHA MONOCLONAL-ANTIBODY IN PATIENTS WITH SEVERE SEPSIS - EFFECTS ON THE CARDIOVASCULAR-SYSTEM AND CYTOKINE LEVELS

In an uncontrolled clinical trial the effects of repeated administrati on of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNFalpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-T NFalpha-antibody intravenously over 5 days using either 1 mg/kg (n = 1 0) or 3 mg/kg (n = 10). The anti-TNFalpha-antibody was well tolerated in all patients without signs of toxicity and without development of a nti-murine antibodies. As assessed by cytokine levels (TNFalpha, Inter leukin-6) and hemodynamics there was no evidence that the higher dosag e of the anti-TNFalpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1 mg/kg per dose). Comparison of our data with recent data from phase I or II trials using a complete murine monoclon al anti-TNFalpha-antibody suggest that the F(ab')2 fragments of the mu rine monoclonal anti-TNFalpha-antibody may be of similar efficacy. Def initive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of la rger ongoing placebo-controlled trials.