Boekstegers P, Weidenhöfer S, Zell R, Pilz G, Holler E, Ertel W, Kapsner T, Redl H, Schlag G, Kaul M
Department of Internal Medicine I, Klinikum Grosshadern, University of Munich, Germany.
Shock. 1994 Apr;1(4):237-45.
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.
在一项非对照临床试验中，对20例严重脓毒症患者研究了重复给予鼠单克隆抗肿瘤坏死因子α（TNFα）抗体（MAK 195F）的F（ab'）2片段对细胞因子水平和心血管系统的影响。患者在5天内静脉内共接受11次单剂量的抗TNFα抗体治疗，剂量分别为1mg/kg（n = 10）或3mg/kg（n = 10）。所有患者对抗TNFα抗体耐受性良好，无毒性迹象，也未产生抗鼠抗体。根据细胞因子水平（TNFα、白细胞介素-6）和血流动力学评估，没有证据表明较高剂量的抗TNFα抗体（每剂量3mg/kg）比较低剂量（每剂量1mg/kg）更有效。将我们的数据与最近使用完整鼠单克隆抗TNFα抗体的I期或II期试验数据进行比较表明，鼠单克隆抗TNFα抗体的F（ab'）2片段可能具有相似的疗效。然而，关于死亡率改善和心血管系统改善的确切结论，有待正在进行的更大规模安慰剂对照试验的结果。
