Does the use of immunoglobulins in very young children hospitalised with a respiratory syncytial virus (RSV) lung infection reduce deaths and hospital stay without increased adverse events, compared with placebo (a similar-appearing fake drug that has no effect)?
Respiratory syncytial virus is a common virus that can infect lungs and airways. Millions of children are treated in hospital each year for RSV, which can result in severe illness and death. The majority of these deaths occur in low-income countries. In high-income countries, the majority of deaths associated with RSV lung infection occur in infants and young children with other illnesses.
Immunoglobulins, also known as antibodies, are a type of molecule normally produced by white blood cells when an infection is present. Immunoglobulins may recognise and attach to viruses (such as RSV) and help destroy them. Immunoglobulins can be produced artificially and given to children who are not making their own RSV antibodies. Some studies have shown that immunoglobulins are helpful in preventing RSV infection in children at high risk of becoming infected. They may also be used as a treatment when an RSV infection is already present, but the effectiveness and safety of immunoglobulins for this use is unknown.
We searched for evidence up to 6 November 2018.
We included seven randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) that compared the effects of immunoglobulins with placebo in 486 young children hospitalised with RSV lung infections. All trials were conducted at sites in the USA; three trials included some children from South American countries (Chile and Panama); and one trial also included children from New Zealand and Australia. The trials were published between 1987 and 2014.
Study funding sources
Five trials were supported by the manufacturer of the immunoglobulin tested in the studies. One trial was supported by a government agency, and one trial did not describe how it was funded.
Immunoglobulins did not appear to be more effective than placebo in preventing deaths among young children with RSV infection, although few deaths occurred in the trials. Immunoglobulins given to children hospitalised with RSV lung infection did not decrease the time spent in hospital. Children treated with immunoglobulins experienced adverse effects of any severity or seriousness and adverse effects considered to be serious (such as respiratory failure) as often as children treated with placebo. There was no difference between immunoglobulins and placebo for any other outcomes measured in the trials, such as the need for oxygen or admission to the intensive care unit. Data from populations in which the rate of death from RSV infection is higher are lacking.
Quality of the evidence
The quality of the evidence was low or very low, which means that the true effect of immunoglobulin treatment for young children in hospital with RSV lung infection may be very different from the findings of this review.
We found insufficient evidence of a difference between immunoglobulins and placebo for any review outcomes. We assessed the evidence for the effects of immunoglobulins when used as a treatment for RSV lower respiratory tract infection in hospitalised infants and young children as of low or very low certainty due to risk of bias and imprecision. We are uncertain of the effects of immunoglobulins on these outcomes, and the true effect may be substantially different from the effects reported in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.
Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin is sometimes used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licenced for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital.
To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections in children aged up to three years, admitted to hospital.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 6 November 2018) with no restrictions. We searched two trial registries for ongoing trials (to 30 March 2018) and checked the reference lists of reviews and included articles for additional studies.
Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence quality using GRADE.
We included seven trials involving 486 infants and children aged up to three years. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. We assessed the primary outcomes of mortality, length of hospital stay, and adverse events as providing low- or very low-certainty evidence due to risk of bias and imprecision. All trials were conducted at sites in high-income countries (USA, Chile, New Zealand, Australia), with two studies including a site in a middle-income country (Panama). Five of the seven studies were "supported" or "sponsored" by the trial drug manufacturers.
We found no evidence of a difference between immunoglobulins and placebo for mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 3 trials; 196 children; 4 deaths; 2 deaths amongst 98 children receiving immunoglobulins, and 2 deaths amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however, the study group of the child was not known and the data were not included in the analysis; very low-certainty evidence), and length of hospitalisation (mean difference −0.70, 95% CI −1.83 to 0.42; 5 trials; 324 children; low-certainty evidence). There was no evidence of a difference between immunoglobulins and placebo in adverse events of any severity or seriousness (reported in five trials) or serious adverse events (four trials) (RR for any severity 1.18, 95% CI 0.78 to 1.78; 340 children; low-certainty evidence, and for serious adverse events 1.08, 95% CI 0.65 to 1.79; 238 children; low-certainty evidence).
We found no evidence of a significant difference between immunoglobulins and placebo for any of our secondary outcomes. We identified one ongoing trial.