Repeated administration of a F(ab')2 fragment of an anti-tumor 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 administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-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-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well tolerated in all patients without signs of toxicity and without development of anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6) and hemodynamics there was no evidence that the higher dosage of the anti-TNF alpha-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 monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.
Boekstegers
P
P
Department of Internal Medicine I, Klinikum Grosshadern, University of Munich, Germany.
Weidenhöfer
S
S
Zell
R
R
Pilz
G
G
Holler
E
E
Ertel
W
W
Kapsner
T
T
Redl
H
H
Schlag
G
G
Kaul
M
M
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002319:Cardiovascular System / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D018805:Sepsis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha