Key messages
-
Palivizumab, when given through the veins or into a muscle (systemically), reduces hospitalisations due to respiratory syncytial virus (RSV) and reduces respiratory problems later on (chest wheezing), but probably results in little to no difference in other outcomes.
-
Palivizumab, when given through the nose (intranasally), may not offer a benefit for most important outcomes.
What is respiratory syncytial virus?
Respiratory syncytial virus (RSV) is the main cause of acute respiratory infections in children, mainly during the first year of life. It accounts for 33 million infections each year, with over 95% of infections occurring in low- and middle-income countries.
What are the symptoms?
Children with RSV may have a runny nose, fever, cough, shortness of breath, wheezing, or difficulty feeding. Infection with RSV may result in hospitalisation, admission to an intensive care unit, and even death, particularly amongst babies younger than two months. Even after the infection, children may have recurrent wheezing and chronic lung problems.
What is palivizumab?
Palivizumab is a medication given into a muscle every month in up to five doses to prevent serious infections in children at high risk for severe disease. It can also be given through the veins or, recently, inside the nose.
What did we want to find out?
We wanted to know the benefits and harms of palivizumab in children at risk of RSV infection.
What did we do?
We looked for studies that compared palivizumab with placebo (dummy treatment), no treatment, or standard care in children at risk of RSV infection.
What did we find?
We found six studies with 3611 children. All studies included a small number of participants, and children with a high risk of poor outcomes if infected with RSV due to underlying health issues, such as premature birth or heart or lung problems. The main results are listed below.
-
Systemic palivizumab reduces hospitalisation due to RSV infection by 56%; based on 98 cases per 1000 participants in the placebo group, this corresponds to 43 per 1000 participants in the palivizumab group. Intranasal palivizumab may increase hospitalisations due to RSV infection, being 2.3 times higher in the palivizumab group (149 per 1000 participants) than in the placebo group (64 per 1000 participants).
-
Palivizumab probably results in little to no difference in death and little to no difference in unwanted effects; based on 23 deaths per 1000 participants and 78 unwanted effects per 1000 participants in the placebo group, this corresponds to 16 deaths per 1000 participants and 84 unwanted effects per 1000 participants in the palivizumab group.
-
Palivizumab probably results in a slight 20% reduction in hospitalisation due to respiratory illness.
-
Systemic palivizumab may reduce the RSV infection rate by 67% at two years’ follow-up, and reduces the number of wheezing days by 61%. In comparison, intranasal palivizumab may increase the RSV infection rate by 64% and may result in little to no difference in wheezing days.
What are the limitations of the evidence?
We are confident that systemic palivizumab reduces hospitalisation due to RSV infection and reduces the number of wheezing days. We are only moderately confident or have little confidence in the remaining evidence because studies were very small/there are not enough studies to be certain about the results.
How up-to-date is the evidence?
The evidence is current to 3 July 2024.
Read the full abstract
Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) 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 during five months in the first RSV season to prevent serious RSV LRTI 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 strategy
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.
Selection criteria
We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history.
Data collection and analysis
We used Cochrane’s Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary 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.
Main results
We included five studies with a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low.
Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 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. 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; 5 studies, 3343 participants; moderate certainty evidence). 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 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) 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 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). 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; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence).
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
