Pediatrics. 1998 Sep;102(3 Pt 1):531-7.
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.
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 approximately 93% received all five scheduled injections.
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.
Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.
确定帕利珠单抗预防高危婴儿因呼吸道合胞病毒（RSV）感染而住院的安全性和有效性。
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至1997年RSV流行季节，1502名早产（小于或等于35周）或患有支气管肺发育不良（BPD）的儿童被随机分组，每30天肌肉注射5次帕利珠单抗（15mg/kg）或等量安慰剂。主要终点是确诊为RSV感染的住院情况。对儿童随访150天（最后一次注射后30天）。对因RSV感染住院的儿童评估其住院总天数、增加吸氧总天数、中度或重度下呼吸道疾病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和中耳炎发生率。安慰剂组和帕利珠单抗组在入组时的人口统计学特征和RSV危险因素方面均衡。两组中99%的儿童完成了方案，约93%的儿童接受了全部5次预定注射。
帕利珠单抗预防使因RSV感染住院的比例降低了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住院的比例降低了78%（8.1%对1.8%）；患有BPD的儿童降低了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。帕利珠单抗组因RSV住院的总天数成比例减少，因RSV住院且吸氧增加的天数减少，因RSV住院且患有中度/重度下呼吸道疾病的天数减少，重症监护病房入院率降低。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。很少有儿童因相关不良事件而停止注射（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和短暂的红斑。安慰剂组1.6%的受试者和帕利珠单抗组3.6%的受试者出现轻度或中度天冬氨酸转氨酶升高；丙氨酸转氨酶的这些百分比分别为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。
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。
