Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants
Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants
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DOI：
10.1542/peds.102.3.531
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发表时间：
1998-09-01
期刊：
影响因子：
8
通讯作者：
Top, FH
中科院分区：
文献类型：
--
作者：
Null, D;Bimle, C;Top, FH
目的：确定帕利珠单抗预防用药在降低高危婴儿因呼吸道合胞病毒（RSV）感染住院发生率方面的安全性和有效性。
方法：在美国、英国和加拿大的139个中心进行了一项随机、双盲、安慰剂对照试验。在1996年至1997年RSV流行季，1502名早产（≤35周）或患有支气管肺发育不良（BPD）的儿童被随机分组，每30天接受一次肌肉注射，共注射5次，分别注射帕利珠单抗（15mg/kg）或等量安慰剂。主要终点是确诊RSV感染的住院情况。对儿童随访150天（从最后一次注射起30天）。对因RSV感染住院的儿童评估其住院总天数、补充氧气增加的总天数、中重度下呼吸道疾病的总天数以及重症监护和机械通气的发生率及总天数。还评估了非RSV引起的呼吸道疾病住院发生率以及中耳炎发生率。安慰剂组和帕利珠单抗组在入组时在人口统计学和RSV危险因素方面均衡。两组中99%的儿童完成了试验方案，约93%的儿童接受了全部5次预定注射。
结果：帕利珠单抗预防使因RSV感染住院的情况减少了55%（安慰剂组为10.6%，帕利珠单抗组为4.8%）。早产但无BPD的儿童因RSV住院的情况减少了78%（8.1%对1.8%）；患有BPD的儿童减少了39%（12.8%对7.9%）。当将性别、入组年龄、入组体重、BPD和胎龄纳入逻辑回归模型时，帕利珠单抗预防的效果仍具有统计学意义。帕利珠单抗组RSV住院总天数、氧气增加的RSV住院天数、中重度下呼吸道疾病的RSV住院天数以及重症监护病房入院率均成比例减少。帕利珠单抗安全且耐受性良好。两组报告的不良事件无显著差异。因相关不良事件停止注射的儿童很少（0.3%）。注射部位反应不常见（安慰剂组为1.8%，帕利珠单抗组为2.7%）；最常见的反应是轻度且短暂的红斑。天冬氨酸氨基转移酶轻度或中度升高在安慰剂组为1.6%，在帕利珠单抗组为3.6%；丙氨酸氨基转移酶的相应百分比分别为2.0%和2.3%。两组中与研究药物相关的肝脏和肾脏不良事件相似。
结论：每月肌肉注射帕利珠单抗对预防早产儿和患有BPD的儿童发生严重RSV疾病是安全有效的。
Objective. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.Methods. A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and similar to 93% received all five scheduled injections.Results. Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BFD.