Garegnani Luis, Roson Rodriguez Pablo, Escobar Liquitay Camila Micaela, Esteban Ignacio, Franco Juan Va
Associate Cochrane Centre, Universidad Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Gavi, the Vaccine Alliance, Geneva, Switzerland.
Cochrane Database Syst Rev. 2025 Jul 23;7(7):CD013757. doi: 10.1002/14651858.CD013757.pub3.
Respiratory viruses are the leading cause of lower respiratory tract infection and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month for five months in the first RSV season to prevent serious RSV lower respiratory tract infection in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children.
To assess the effects of palivizumab in preventing severe RSV infection in children.
We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, Scopus, and two trials registers from the inception of each database to July 2024 with no language or publication status restrictions.
We included randomised controlled trials (RCTs) and cluster-RCTs in children 0 to 24 months of age of any gender, regardless of RSV infection history, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention, or standard care.
The critical outcomes were hospitalisation due to RSV infection, all-cause mortality, and adverse events. Important outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay, and mechanical ventilation days.
We used Cochrane's RoB 2 tool to assess risk of bias.
We conducted meta-analyses using random-effects models to calculate risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence for each outcome.
We included one new trial in this update, bringing the total number of RCTs to six studies with 3611 children. All studies were parallel RCTs assessing the effects of 15 mg/kg of palivizumab every month for up to five months, compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants, and another study administered palivizumab intranasally. Most of the included studies were conducted in children with a high risk of severe RSV infection due to comorbidities like bronchopulmonary dysplasia or congenital heart disease.
Systemic palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (RR 0.44, 95% CI 0.30 to 0.64; I² = 23%; 5 studies, 3343 participants; high-certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Intranasal palivizumab may increase hospitalisation due to RSV infection compared to placebo or no intervention at two years' follow-up (RR 2.33, 95% CI 0.64 to 8.48; 1 study, 94 participants; low-certainty evidence due to serious concerns about imprecision). Based on 64 hospitalisations per 1000 participants in the placebo group, this corresponds to 149 (41 to 541) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; I² = 0%; 5 studies, 3343 participants; moderate-certainty evidence due to concerns about imprecision). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.08, 95% CI 0.85 to 1.38; I² = 0%; 4 studies, 3099 participants; moderate-certainty evidence due to concerns about imprecision). Based on 78 cases per 1000 participants in the placebo group, this corresponds to 84 (66 to 107) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.80, 95% CI 0.65 to 0.99; I² = 41%; 6 studies, 3437 participants; moderate-certainty evidence due to concerns about imprecision). Systemic palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; I² = 0%; 3 studies, 554 participants; low-certainty evidence due to serious concerns about imprecision). Intranasal palivizumab may increase RSV infection compared to placebo or no intervention at two years' follow-up (RR 1.64, 95% CI 0.87 to 3.08; 1 study, 94 participants; low-certainty evidence due to serious concerns about imprecision). Systemic palivizumab also reduces the number of wheezing days at one-year follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high-certainty evidence). Intranasal palivizumab may result in little to no difference in the mean fraction of wheezing days (mean fraction of wheezing days of 0.94, 95% CI -1.9 to 3.5; 1 study, 93 participants; low-certainty evidence). The risk of bias in outcomes across all studies was similar and predominantly low.
AUTHORS' CONCLUSIONS: Based on the available evidence, prophylaxis with systemic palivizumab reduces hospitalisation due to RSV infection and probably results in little to no difference in mortality. Intranasal palivizumab may increase hospitalisation due to RSV infection. Palivizumab probably results in little to no difference in adverse events. Moreover, palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness. Systemic palivizumab may result in a large reduction in RSV infections, whilst intranasal palivizumab may increase RSV infection. Systemic palivizumab also reduces the number of wheezing days, whilst intranasal palivizumab may result in little to no difference in the mean fraction of wheezing days. These results may be applicable to children with a high risk of severe RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab in children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.
This Cochrane review had no dedicated funding.
Protocol (2020): doi.org/10.1002/14651858.CD013757 First review version (2021): doi.org/10.1002/14651858.CD013757.pub2.
呼吸道病毒是婴幼儿下呼吸道感染和住院的主要原因。呼吸道合胞病毒（RSV）是该人群中的主要感染源。在首个RSV季节，帕利珠单抗每月肌肉注射一次，共注射五个月，以预防儿童严重的RSV下呼吸道感染。鉴于其成本高昂，了解帕利珠单抗在预防儿童严重RSV疾病方面是否仍然有效至关重要。
评估帕利珠单抗在预防儿童严重RSV感染中的效果。
我们检索了Cochrane系统评价数据库、MEDLINE、Embase、拉丁美洲及加勒比地区卫生科学数据库、护理及健康照护领域数据库、Scopus以及两个试验注册库，检索时间从各数据库建库起至2024年7月，无语言或发表状态限制。
我们纳入了0至24个月龄、任何性别的儿童的随机对照试验（RCT）和整群随机对照试验，无论其RSV感染史如何，比较每月一次给予15mg/kg剂量（最大五剂）的帕利珠单抗与安慰剂、无干预措施或标准治疗。
关键结局指标为因RSV感染住院、全因死亡率和不良事件。重要结局指标为因呼吸道相关疾病住院、住院时间、RSV感染、喘息天数、吸氧天数、重症监护病房住院时间和机械通气天数。
我们使用Cochrane的RoB 2工具评估偏倚风险。
我们采用随机效应模型进行荟萃分析，计算二分结局的风险比（RR）和连续结局的平均差（MD），两者均带有95%置信区间（CI）。我们使用GRADE评估每个结局的证据确定性。
本次更新纳入了一项新试验，使RCT的总数达到六项研究，涉及3611名儿童。所有研究均为平行RCT，评估每月给予15mg/kg帕利珠单抗最多五个月的效果，与门诊环境中的安慰剂或无干预措施进行比较，尽管一项研究还纳入了住院婴儿，另一项研究采用鼻内给予帕利珠单抗。大多数纳入研究是在因支气管肺发育不良或先天性心脏病等合并症而有严重RSV感染高风险的儿童中进行的。
在两年随访期内，全身应用帕利珠单抗可降低因RSV感染导致的住院率（RR 0.44，95%CI 0.30至0.64；I² = 23%；5项研究，3343名参与者；高确定性证据）。基于安慰剂组每1000名参与者中有98例住院，这相当于帕利珠单抗组每1000名参与者中有43例（29至62例）住院。在两年随访期内，与安慰剂或无干预措施相比，鼻内应用帕利珠单抗可能会增加因RSV感染导致的住院率（RR 2.33，95%CI 0.64至8.48；1项研究，94名参与者；由于对精确性的严重担忧，证据确定性低）。基于安慰剂组每1000名参与者中有64例住院，这相当于帕利珠单抗组每1000名参与者中有149例（41至541例）住院。在两年随访期内，帕利珠单抗可能对死亡率影响甚微或无差异（RR 0.69，95%CI 0.42至1.15；I² = 0%；
