title: A population-weighted, condition-adjusted estimate of palivizumab efficacy in preventing RSV-related hospitalizations among US high-risk children.
abstract: Preterm infants ≤ 35 weeks' gestational age (GA), and children ≤ 24 months of age with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart disease (hsCHD) are at high risk for developing severe respiratory syncytial virus (RSV) disease. In 3 previous randomized, placebo-controlled trials, palivizumab efficacy varied significantly based on these underlying conditions, and trial enrollment was not proportional to condition prevalence. This analysis provides the first estimate of the population-weighted efficacy of palivizumab in high-risk children, adjusting for condition prevalence. Palivizumab efficacy by high-risk condition was obtained from the clinical trials. The annual number of US children with each condition was obtained from the 2010 Centers for Disease Control and Prevention (CDC) natality statistics and the medical literature. Data from specialty pharmacies in the US palivizumab distribution network were used to estimate the population for each condition receiving at least 1 dose in the outpatient setting in 2012-2013. The weighted efficacy estimate was derived by summing the products of the condition-specific relative risk reductions and the relative frequency of each condition among those receiving palivizumab. The US population-weighted efficacy estimate for those receiving palivizumab was 68%. Due to the low prevalence of BPD and hsCHD and the higher efficacy observed in preterm infants without BPD or CHD, the population-weighted estimate of palivizumab efficacy is higher than the overall 45-55% efficacy observed in initial clinical trials. Consistent with 2012 American Academy of Pediatrics RSV prophylaxis recommendations, a low proportion of preterm infants 32-35 weeks' gestational age receive palivizumab.
authors.affiliation: a AstraZeneca ; Gaithersburg , MD USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ambrose
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Veena R
authors.initials: VR
authors.lastname: Kumar
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology; D006330:Heart Defects, Congenital / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D000069455:Palivizumab; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses; D012306:Risk; D012307:Risk Factors; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D000069455:Palivizumab
keywords: BPD, bronchopulmonary dysplasia; CDC, Centers for Disease Control and Prevention; CHD, congenital heart disease; FDA, US Food and Drug Administration; GA, gestational age; RSV, respiratory syncytial virus; RSV-related hospitalization; RSVH, respiratory syncytial virus-related hospitalization; condition-adjusted efficacy; efficacy; hsCHD, hemodynamically significant congenital heart disease; palivizumab; population-weighted efficacy; respiratory syncytial virus; severe RSV disease