Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children

Abstract

Background Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections, resulting in about 3.4 million hospitalisations annually in children under five. Palivizumab is the only product approved for prevention of serious RSV disease, as motavizumab is no longer being developed for this condition. The efficacy and safety of palivizumab has been evaluated in randomized controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost‐effectiveness. Objectives To assess the effectiveness and safety of palivizumab prophylaxis in reducing the risk of complications (hospitalization due to RSV infection) in high‐risk infants and children. To assess the cost‐effectiveness (or cost‐utility) of palivizumab prophylaxis in infants and children in different risk groups. Search methods We searched CENTRAL (2012, Issue 7), MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for RCTs. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012), Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for EEs. Selection criteria We included RCTs comparing palivizumab prophylaxis with a placebo or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost‐effectiveness analyses and cost‐utility analyses comparing palivizumab prophylaxis with no prophylaxis. Data collection and analysis Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). For continuous outcomes, we provided a narrative summary of results due to missing data on standard deviations. We performed fixed‐effect meta‐analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost‐effectiveness and/or cost‐utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies. Main results Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but most of the outcomes assessed relied on data from only two studies. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) and a statistically non‐significant reduction in all‐cause mortality (RR 0.69, 95% CI 0.42 to 1.15) ...

Where are we with RSV prophylaxis?: Table 1

“…Bronchiolitis is a combined upper and lower respiratory tract infection resulting in increased airway secretions, and bronchospasm causing shortness of breath and wheeze. Mild cases can be nursed at home, but 2%–3% may be admitted to hospital 6 7. National Institute for Health and Care Excellence guidelines for bronchiolitis detail what to consider when assessing individuals and their need for hospital care (see table 1).…”

“…Other countries, such as Italy and USA include attendance at community settings or cohabitees younger than 5 years as risk factors 7. Other risks may include parental smoking, day care attendance, overcrowding, being fed formula rather than breast milk, male sex, lower socioeconomic class and admission to hospital during the RSV season 3 6 11…”

Preventing severe respiratory syncytial virus disease: passive, active immunisation and new antivirals

“…A recent Cochrane systematic review analysed data from three RCTs (including those described above) comparing palivizumab with placebo (n=2831) and four RCTs comparing palivizumab with motavizumab (n=8265), among infants born preterm, with congenital heart disease or chronic lung disease 18. They concluded that prophylaxis compared to placebo was associated with a 51% reduction in risk of RSV hospitalisation (RR=0.49 95% CI 0.37 to 0.64) and a 50% reduction in admissions to intensive care units (RR=0.50 95% CI 0.30 to 0.81).…”

“…They concluded that prophylaxis compared to placebo was associated with a 51% reduction in risk of RSV hospitalisation (RR=0.49 95% CI 0.37 to 0.64) and a 50% reduction in admissions to intensive care units (RR=0.50 95% CI 0.30 to 0.81). In addition, pooled analysis revealed a reduction in all-cause mortality, though this was statistically non-significant (RR=0.69 95% CI 0.42 to 1.15) 18. It is perhaps most useful though to consider the number of children that need to be treated to prevent a hospital episode.…”

“…The most recent review of the economic evidence concluded that the cost-effectiveness of palivizumab is inconsistent across different studies—depending on the threshold used and the consumption of healthcare resources taken into consideration 18. In addition, when interpreting cost-effectiveness studies the different average weights of infants used in the analysis should be carefully examined as this can have a considerable effect on the conclusions reached.…”