呼吸道合胞病毒单克隆抗体尼塞韦单抗免疫接种与安慰剂对照后的下呼吸道感染：一项3期随机临床试验（MELODY）的分析

Lower respiratory tract infections following respiratory syncytial virus monoclonal antibody nirsevimab immunization versus placebo: Analysis from a Phase 3 randomized clinical trial (MELODY).

作者信息

Arbetter Doug, Gopalakrishnan Vancheswaran, Aksyuk Anastasia A, Ahani Bahar, Chang Yue, Dagan Ron, Esser Mark T, Hammitt Laura L, Mankad Vaishali S, Saez-Llorens Xavier, Shen David, Leach Amanda, Kelly Elizabeth J, Villafana Tonya, Wilkins Deidre

机构信息

Biometrics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.

Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

出版信息

Clin Infect Dis. 2024 Dec 4. doi: 10.1093/cid/ciae596.

DOI:10.1093/cid/ciae596

PMID:39656748

Abstract

BACKGROUND

Nirsevimab is an extended half-life, highly potent neutralizing monoclonal antibody against the respiratory syncytial virus (RSV) fusion protein, with efficacy in preventing RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post-hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab, in healthy-term and late-preterm (i.e. gestational age ≥35 weeks) infants entering their first RSV season (MELODY).

METHODS

3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants presenting with an LRTI and tested for 22 different respiratory pathogens using the BioFire® Respiratory 2.1 Panel. Incidence of RSV and non-RSV MA-LRTIs through Day 511 and LRTI severity per the ReSViNET scale were assessed.

RESULTS

852 nasopharyngeal swabs were collected from 561 participants through Day 511: 519 swabs from 337 nirsevimab participants and 333 swabs from 224 placebo participants. RSV and non-RSV infections were detected in 193/852 (22.7%) and 551/852 (64.7%) swabs, respectively. RSV infection rates were lower with nirsevimab compared with placebo, including RSV-rhinovirus/enterovirus coinfections. Rates of other viral infections were similar between study arms. Approximately 70% of single RSV infections and RSV coinfections were adjudicated as mild, and 26.2% of single RSV infections and 24.5% of RSV coinfections required hospitalization.

CONCLUSIONS

Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses.

TRIAL REGISTRATION

ClinicalTrials.gov NCT03979313.

摘要

背景

尼塞韦单抗是一种半衰期延长、高效的抗呼吸道合胞病毒（RSV）融合蛋白的中和单克隆抗体，在预防婴儿和医学上易感染儿童（年龄≤24个月）的RSV相关的需要就医（MA）的下呼吸道感染（LRTI）方面具有疗效。这项事后探索性分析在一项针对进入首个RSV季节的足月儿和晚期早产儿（即胎龄≥35周）的尼塞韦单抗2:1随机、双盲、安慰剂对照3期研究（MELODY）中，考察了RSV和其他呼吸道病原体导致的LRTI发病率。

方法

3012名参与者被随机分配至尼塞韦单抗组（n = 2009）或安慰剂组（n = 1003）。从出现LRTI的婴儿中采集鼻咽拭子，并使用BioFire® Respiratory 2.1 Panel检测22种不同的呼吸道病原体。评估至第511天RSV和非RSV MA-LRTI的发病率以及根据ReSViNET量表评估的LRTI严重程度。

结果

至第511天，从561名参与者中采集了852份鼻咽拭子：337名尼塞韦单抗参与者的519份拭子和224名安慰剂参与者的333份拭子。在193/852（22.7%）和551/852（64.7%）份拭子中分别检测到RSV和非RSV感染。与安慰剂相比，尼塞韦单抗组的RSV感染率较低，包括RSV-鼻病毒/肠道病毒合并感染。研究组之间其他病毒感染率相似。约70%的单一RSV感染和RSV合并感染被判定为轻度，26.2%的单一RSV感染和24.5%的RSV合并感染需要住院治疗。