RATIONALE: 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.
OBJECTIVES: To assess the effects of palivizumab in preventing severe RSV infection in children.
SEARCH METHODS: 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.
ELIGIBILITY CRITERIA: 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.
OUTCOMES: 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.
RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias.
SYNTHESIS METHODS: 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.
INCLUDED STUDIES: 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.
SYNTHESIS OF RESULTS: 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.
FUNDING: This Cochrane review had no dedicated funding.
REGISTRATION: Protocol (2020): doi.org/10.1002/14651858.CD013757 First review version (2021): doi.org/10.1002/14651858.CD013757.pub2.
