Nirsevimab reduces the risk of a medically attended visit for respiratory syncytial virus

Reference

Hammitt LL, Dagan R, Yuan Y, et al, for the MELODY Study Group. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med 2022;386(9):837-846.

Synopsis

Injection of monoclonal antibodies, such as palivizumab or nirsevimab, to prevent respiratory syncytial virus (RSV) in preterm, high-risk infants has been shown to be effective. This is the first study of nirsevimab in healthy infants born at 35 weeks' gestation or later. The researchers randomized (in a 2:1 ratio) 1490 healthy infants younger than 1 year who were entering their first RSV season to receive nirsevimab or placebo. Infants were excluded if they met criteria for administration of the currently approved drug palivizumab or if they had a previous RSV infection. The dose was 50 mg if the infant weighed less than 5 kg or 100 mg if the infant weighed 5 kg or more and was given only once (palivizumab requires monthly injections). Groups were balanced at the beginning of the study, and analysis was by intention to treat. Most infants were younger than 3 months, 86% were 37 weeks' gestation or more at birth, and 28% were Black. Follow-up was good, with 98% followed up for 150 days and 92% for 1 year. A medically attended visit for RSV was less likely in the nirsevimab group (1.2% vs 5.0%; P < .001; number needed to treat [NNT] = 26). There was no significant difference in hospitalizations between groups, though there was clearly a strong trend (0.6% vs 1.6%; P = .07). The authors did several post hoc analyses (ie, data dredging) to try to find additional measures of efficacy. Best to ignore those. Adverse events were mild and similar between groups. They also did a pooled analysis combining data from the previous study in preterm infants with the results of this study and found a significant reduction in hospitalizations — but this is completely irrelevant to the question of whether it prevents hospitalization in healthy term infants. Pre-specifying an inappropriate analysis does not make it valid.