Review question
What are the effects (benefits and harms) of palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children?
Background
RSV is the main cause of acute respiratory infections in children, mainly during the first year of life, accounting for 33.1 million infections a year with an estimated 90.6% of these episodes occurring in low- and middle-income countries. These infections may present with a runny nose, fever, cough, shortness of breath, wheezing, or difficulty feeding. They may result in hospitalisation, admission to an intensive care unit, and even death, in particular amongst infants aged less than two months, with an estimated hospitalisation rate of 1970 per 100,000 population and 59,600 deaths annually worldwide in children younger than five years old. They may also lead to long-term complications such as recurrent wheezing and chronic lung problems.
Palivizumab, sold under the brand name Synagis, is a drug administered with an intramuscular injection every month up to five doses to prevent serious infections in children at high risk for severe disease.
Search date
The evidence is current to 14 October 2021.
Study characteristics
We included five studies with 3343 participants. All studies included a small number of participants, including children with a high risk of adverse outcomes if infected with RSV due to underlying health issues, such as premature birth or heart or pulmonary problems.
Study funding sources
Most studies did not specify their funding sources. One study was funded by Abbott Laboratories and by the Netherlands Organisation for Health Research and Development.
Key results
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. Palivizumab probably results in little to no difference in mortality, and little to no difference in adverse events; based on 23 deaths per 1000 participants and 84 adverse events per 1000 participants in the placebo group, this corresponds to 16 deaths per 1000 participants and 81 adverse events per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory illness by 22% but may result in little to no difference in length of hospital stay. It may reduce RSV infection rate by 67% at two years’ follow-up. Palivizumab also reduces the number of wheezing days by 61% but may result in little to no difference in days using oxygen, length of stay in the intensive care unit, or mechanical ventilation days.
Certainty of the evidence
The overall certainty of the evidence was moderate to high.
The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities.
Further research is needed to establish the effect of palivizumab on 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.
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.
To assess the effects of palivizumab for preventing severe RSV infection in children.
We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021.
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.
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.
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).