Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy statement in 1998. Guidance initially was based on the result from a single randomized, placebo-controlled clinical trial conducted in 1996–1997 describing an overall reduction in RSV hospitalization rate from 10.6% among placebo recipients to 4.8% among children who received prophylaxis. The results of a second randomized, placebo-controlled trial of children with hemodynamically significant heart disease were published in 2003 and revealed a reduction in RSV hospitalization rate from 9.7% in control subjects to 5.3% among prophylaxis recipients. Because no additional controlled trials regarding efficacy were published, AAP guidance has been updated periodically to reflect the most recent literature regarding children at greatest risk of severe disease. Since the last update in 2012, new data have become available regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effects of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, and the effect of prophylaxis on wheezing and palivizumab-resistant RSV isolates. These data enable further refinement of AAP guidance to most clearly focus on those children at greatest risk. Pediatrics 2014;134:e620–e638 Palivizumab is a humanized mouse immunoglobulin (IgG1) monoclonal antibody produced by recombinant DNA technology. The antibody is directed against a conserved epitope of the A antigenic site of the fusion (F) protein of respiratory syncytial virus (RSV) and demonstrates both neutralizing and fusion inhibitory activity.1 The antibody consists of 2 heavy chains and 2 light chains; 95% of the amino acid sequences (framework) are of human origin, and 5% (antigen binding sites) are of mouse origin. After intramuscular administration, palivizumab is distributed hematogenously throughout the body, including the lower respiratory tract. When RSV encounters palivizumab in the lower respiratory tract, antibody binds to F protein and prevents the structural COMMITTEE ON INFECTIOUS DISEASES and BRONCHIOLITIS GUIDELINES COMMITTEE