UASSIGNED:呼吸道合胞病毒(RSV)是5岁以下儿童急性下呼吸道感染的主要原因;迫切需要有效的预防策略。
UNASSIGNED:比较单克隆抗体预防婴儿和儿童RSV感染的功效和安全性。
未经评估:在本系统综述和网络荟萃分析中,PubMed,Embase,中部,和ClinicalTrials.gov从数据库开始到2022年3月进行了搜索。
UNASSIGNED:纳入RSV感染高危婴儿接受单克隆抗体或安慰剂的随机临床试验。与单克隆抗体相关的关键词和广泛的词汇,RSV,并检索随机临床试验。
UNASSIGNED:使用系统评价和Meta分析报告指南的首选报告项目。由2名审稿人组成的团队独立进行文献筛选,数据提取,和偏见风险评估。建议的分级,评估,事态发展,并采用评估方法对证据的确定性进行评级。在频率论框架下使用一致性模型进行了随机效应模型网络元分析。
未经评估:主要结果是全因死亡率,RSV相关住院,RSV相关感染,与药物相关的不良事件,重症监护室入院,补充氧气的使用,和机械通风使用。
UNASSIGNED:15项随机临床试验符合资格,涉及18395名参与者;14项合成,共有18042名参与者(进入研究时的平均年龄,3.99个月[IQR,3.25-6.58个月];男性比例中位数,52.37%[IQR,50.49%-53.85%])。与安慰剂相比,有中等到高确定性的证据,nirsevimab,帕利珠单抗,和motavizumab与每1000名参与者中RSV相关的感染显着减少相关(nirsevimab:-123[95%CI,-138至-100];帕利珠单抗:-108[95%CI,-127至-82];motavizumab:-136[95%CI,-146至-125])和RSV相关的住院率(nirsevima有了中等确定性的证据,motavizumab和palivizumab均与每1000名参与者的重症监护病房入院显着减少相关(-8[95%CI,-9至-4]和-5[95%CI,-7至0],分别)和每1000名参与者的补充氧气使用量(-59[95%CI,-63至-54]和-55[95%CI,-61至-41],分别),和nirsevimab与每1000名参与者的补充氧气使用显著减少相关(-59[95%CI,-65~-40]).全因死亡率和药物相关不良事件无显著差异。Suptavumab对感兴趣的结果没有显示出任何显著的益处。
未经批准:在这项研究中,莫维珠单抗,nirsevimab,和帕利珠单抗与预防RSV感染的实质性益处相关,与安慰剂相比,不良事件没有显著增加。然而,需要更多的研究来证实目前的结论,特别是安全性和成本效益。
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.
To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.
In this systematic
review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.
Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.
The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.
Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.
In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.