Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.

Palivizumab (Synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (LRTIs) caused by respiratory syncytial virus (RSV). RSV is the leading cause of hospitalization for LRTIs in infants, causing winter- or wet-season epidemics. In two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced RSV-related hospitalizations by 55% in 1502 infants with prematurity and/or bronchopulmonary dysplasia/chronic lung disease (BPD/CLD) and by 45% in 1287 infants with hemodynamically significant congenital heart disease (HSCHD). Reductions were statistically significant versus placebo in infants with BPD/CLD, with all degrees of prematurity, and with acyanotic/other heart disease. Palivizumab was generally well tolerated, with < or =1.9% of recipients discontinuing treatment for tolerability reasons. In placebo-controlled trials, the most common potentially drug-related adverse events were fever, nervousness, injection-site reactions, and diarrhea. Drug-related events occurred in 7.2-11% of palivizumab recipients in controlled trials (vs 6.9-10% with placebo) and 0-7.9% in open-label trials. Very few serious potentially drug-related adverse events occurred in clinical trials; four occurred in 2 of 285 patients in one open-label trial. No significant anti-palivizumab antibodies developed during palivizumab use. Palivizumab trough serum concentrations were below the recommended 40 microg/mL in about 33% and up to 14% of children prior to their second and third palivizumab injections. In pharmacoeconomic studies, the cost of palivizumab per hospitalization averted was generally lowest in the highest-risk infants. Drug cost was generally the most influential factor in sensitivity analyses. In conclusion, prophylaxis with palivizumab significantly reduces the incidence of RSV-related hospitalization relative to placebo and is generally well tolerated in high-risk infants aged <2 years, including those with prematurity and BPD/CLD or HSCHD, which are risk factors for early or serious RSV infection. Palivizumab is approved for use in these patients. Other high-risk infants in whom palivizumab has not been formally assessed, such as those with immunodeficiency, cystic fibrosis, or location-specific risk factors (including extended hospital stays) might potentially benefit from palivizumab. The use of palivizumab in these other high-risk populations is likely to be determined as much by pharmacoeconomic considerations as by efficacy outcomes.