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) ...

Prematurity and the burden of influenza and respiratory syncytial virus disease

“…in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease or those born preterm. [125] In conclusion, we found the burden of respiratory morbidity being generally high in former preterm infants and aggravated in those with BPD. Influenza virus infection plays a minor role compared with RSV associated respiratory tract infection during infancy and early childhood.…”

Oral GS-5806 Activity in a Respiratory Syncytial Virus Challenge Study

“…11,12,16,17 Palivizumab, an RSV-specific monoclonal antibody approved for the prevention of RSV infection, is only partially effective (reducing RSV hospitalization rates only by approximately 60%) 16 and is indicated only for the 3% of the total infant population who are born prematurely or have underlying conditions (chronic lung disease, congenital heart disease, immunodeficiencies, or other severe chronic illnesses). 5,16,[18][19][20] GS-5806 is a novel oral small molecule that inhibits RSV entry at low nanomolar concentrations by blocking viral-envelope fusion with the host-cell membrane (for details see the Supplementary Appendix, available with the full text of this article at NEJM.org). A phase 1 study in humans showed that a single dose of 300 mg and multiple doses of up to 75 mg daily for 7 days were not associated with notable adverse events.…”

Chemotherapy of respiratory syncytial virus infections: the final breakthrough

“…(For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) of the total infant population who are born prematurely or who have underlying conditions (chronic lung disease, congenital heart disease, immunodeficiencies or other severe chronic illnesses) [17]. RSV infection in early childhood is associated with recurrent wheezing later in life [9], and palivizumab treatment in otherwise healthy preterm infants results in a significant reduction in wheezing during the first year of life, even after the end of treatment [9].…”

“…Palivizumab is the only product approved for the prevention of serious RSV disease [17] and, based on seven studies (all sponsored by the drug manufacturing company) involving 11 096 patients, palivizumab would have a favourable preventive effect in children who are at high risk of acquiring severe RSV infection compared with placebo [17], but due to the high costs of the drug, the question remains whether the drug is cost effective [18].…”