Raxibacumab for the Treatment of Inhalational Anthrax.
Raxibacumab for the Treatment of Inhalational Anthrax.
复制标题
DOI：
10.1056/nejmoa0810603
复制
发表时间：
2009-07-09
影响因子：
158.5
通讯作者：
Bolmer, Sally D.
中科院分区：
文献类型：
--
作者：
Migone, Thi-Sau;Subramanian, G. Mani;Bolmer, Sally D.
背景：由炭疽芽孢杆菌引起的吸入性炭疽病具有很高的死亡率，主要是由于毒素介导的损伤。Raxibacumab是一种针对炭疽毒素保护性抗原的人IgG1(Lamda)单抗。方法：我们在兔子和猴子身上进行了四项随机、安慰剂对照研究，评估了raxibacumab作为预防药物和发病后的有效性。动物暴露在炭疽芽胞的雾化靶标暴露中，大约是(在预防研究中)和(在治疗干预研究中)中致死剂量的100倍和200倍。在治疗干预研究中，动物被监测症状的出现。血清中可检测到保护性抗原、体温显著升高或两者兼有的动物接受单次静脉注射安慰剂或raxibacumab，剂量为每公斤体重20毫克或每公斤40毫克。主要终点是第14天(兔子)或第28天(猴子)的存活。结果：在兔和猴中，保护性抗原检测时间与菌血症发生时间呈正相关(r=0.9，P
Background: Inhalational anthrax caused by Bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. Raxibacumab is a human IgG1(lamda) monoclonal antibody directed against protective antigen, a component of the anthrax toxin.Methods: We evaluated the efficacy of raxibacumab as a prophylactic agent and after disease onset in a total of four randomized, placebo-controlled studies conducted in rabbits and monkeys. Animals were exposed to an aerosolized target exposure of B. anthracis spores that was approximately 100 times (in the prophylactic studies) and 200 times (in the therapeutic-intervention studies) the median lethal dose. In the therapeutic-intervention studies, animals were monitored for the onset of symptoms. Animals with detectable protective antigen in serum, a significant increase in temperature, or both received a single intravenous bolus of placebo or raxibacumab at a dose of either 20 mg per kilogram of body weight or 40 mg per kilogram. The primary end point was survival at day 14 (in rabbits) or at day 28 (in monkeys). Safety studies were conducted with intravenous raxibacumab (40 mg per kilogram) in 333 healthy human volunteers.Results: In both rabbits and monkeys, the time to detection of protective antigen correlated with the time to bacteremia (r=0.9, P