PDF(Pubmed)
Abstract：
BACKGROUND: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks\' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA).
METHODS: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab.
RESULTS: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment.
CONCLUSIONS: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.
METHODS: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab.
RESULTS: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment.
CONCLUSIONS: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.
摘要：
背景：Nirsevimab在美国被批准用于预防第一个RSV季节期间的新生儿和婴儿以及年龄≤24个月的儿童的呼吸道合胞病毒（RSV）下呼吸道疾病，这些儿童在第二个RSV季节仍然容易受到严重RSV疾病的影响。我们总结了来自三个随机对照试验的nirsevimab安全性数据的预先指定分析：2b期（NCT02878330；出生≥29至<35周的健康婴儿[wGA]）；3MELODY期（NCT03979313；出生≥35wGA的健康婴儿）；和2/3MEDLEY期（NCT03959488；患有先天性心脏病或≤35岁的婴儿。
方法：参与者（随机2：1）接受单次肌内剂量的nirsevimab或比较剂（安慰剂，2b期/MELODY；5×每月一次帕利珠单抗，MEDLEY）在他们的第一个RSV赛季之前（接受者<5公斤，nirsevimab50mg；≥5kg，nirsevimab100毫克）。在Medley,CHD/CLD患儿持续到第二个RSV季节:第一个季节的nirsevimab接受者接受了200mg的nirsevimab;第一个季节的palivizumab接受者被1:1重新随机分配接受200mg的nirsevimab或5次每月一次的palivizumab.
结果：发病率，严重程度,和AE的性质在不同的治疗中相似(nirsevimab，n=3184；安慰剂，n=1284；帕利珠单抗，n=304)。大多数不良事件的严重程度为轻度至中度，≥98%与治疗无关。特别关注的AE很少发生（<1％）：没有过敏反应或血小板减少症与治疗相关，没有免疫复合物疾病的报道。死亡（发生率<1.0%）均与治疗无关。
结论：每个季节单剂量的尼尔塞维玛用于预防RSV疾病具有良好的安全性。无论WGA或合并症。
方法：参与者（随机2：1）接受单次肌内剂量的nirsevimab或比较剂（安慰剂，2b期/MELODY；5×每月一次帕利珠单抗，MEDLEY）在他们的第一个RSV赛季之前（接受者<5公斤，nirsevimab50mg；≥5kg，nirsevimab100毫克）。在Medley,CHD/CLD患儿持续到第二个RSV季节:第一个季节的nirsevimab接受者接受了200mg的nirsevimab;第一个季节的palivizumab接受者被1:1重新随机分配接受200mg的nirsevimab或5次每月一次的palivizumab.
结果：发病率，严重程度,和AE的性质在不同的治疗中相似(nirsevimab，n=3184；安慰剂，n=1284；帕利珠单抗，n=304)。大多数不良事件的严重程度为轻度至中度，≥98%与治疗无关。特别关注的AE很少发生（<1％）：没有过敏反应或血小板减少症与治疗相关，没有免疫复合物疾病的报道。死亡（发生率<1.0%）均与治疗无关。
结论：每个季节单剂量的尼尔塞维玛用于预防RSV疾病具有良好的安全性。无论WGA或合并症。
