Immunoglobulin treatment for hospitalised infants and young children with respiratory syncytial virus infection

Abstract

Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and currenttherapies (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 improveoutcomes when used as a treatment for establishedRSV infection in infants and young children admitted to hospital. OBJECTIVES: To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infectionsin children aged up to three years, admitted to hospital. SEARCH METHODS: We searched theCochrane 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 twotrial registries for ongoing trials (to 30 March 2018) and checked the referencelists of reviews and included articles for additional studies. Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and childrenaged up to three years with laboratory-diagnosed RSVlower 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 wereconducted 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 differencebetween 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. 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 forRSV 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 datafrom populations in which the rate of death from RSV infection is higher are lacking.