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

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) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90) and a non-significant risk reduction in all-cause mortality (RR 0.74, 95% CI 0.38 to 1.43). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups.

We included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to large differences in the results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors, and on the cost-effectiveness threshold set by the healthcare sector in each country.

Authors' conclusions

There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease, or those born preterm.

Results from economic evaluations of palivizumab prophylaxis are inconsistent across studies, ranging from highly cost-effective to not cost-effective, implying that economic findings must be interpreted with caution. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.

Plain Language Summary

Palivizumab for reducing the risk of severe RSV infection in children

Respiratory syncytial virus (RSV) infection is a major cause of acute respiratory infections in children. RSV infection can lead to morbidity and mortality in children, resulting in hospitalization, admission to an intensive care unit, the need for intensive medical therapies and death.

Most infected children suffer little consequence. However, children who have other serious health problems are known to be at higher risk of complications from RSV infection. This review examined the use of a passive immunisation - palivizumab - to prevent and modify the severity of RSV infection in these children and to determine if it is cost-effective.

The results from this review are based on data from seven studies (all sponsored by the drug manufacturing company) involving 11,096 participants reporting on efficacy and safety of palivizumab, and 34 studies reporting on its cost-effectiveness.

Our findings suggest a favorable effect of preventive use of palivizumab in children who are at higher risk of acquiring severe RSV infection, when compared to placebo. Children treated with palivizumab were less often hospitalised, spent fewer days in the hospital, were admitted to an intensive care unit less often, and had fewer days of oxygen therapy than children who received a placebo.

Considering the underlying health problems in this population of infants and children, high rates of adverse events are quite expected. Our findings showed that children treated with palivizumab experienced adverse events similarly as often as children treated with placebo.

Palivizumab was shown to be effective in reducing the hospitalisations, but whether it is also cost-effective is not easy to determine. This review found large differences in cost-effectiveness results across the studies. Due to the high costs of the drug, in many countries palivizumab prophylaxis might not be available as a standard treatment.