*Study group or publication referenced by American Academy of Pediatrics Committee on Infectious Diseases 2009 Policy Statement for Palivizumab.5Additional data were provided by BS Rodgers-Gray by personal communication on July 3, 2013. An important bias to consider in evaluating these studies is exposure time. for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season. Keywords:palivizumab, preterm infants, monthly dosing, guidelines, respiratory syncytial virus == Introduction == Palivizumab, an IgG1 monoclonal antibody, is approved for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease. Palivizumab provides passive immunity through a dosing regimen of 15 mg/kg monthly throughout the RSV season. To control drug costs, some guideline bodies have attempted to amend this approved dosing regimen. Current American Academy of Pediatrics (AAP) guidelines1for RSV prophylaxis with palivizumab in the US and the British Columbia Immunoprophylaxis Committee guidelines2in British Columbia, Canada, recommend less than full-season dosing for some or all high-risk infants. These variations generally assume that the RSV protection threshold for palivizumab is well defined, is similar for all patients, and that palivizumab behaves pharmacokinetically like a small molecule drug or medication. The NGD-4715 variations in the dosing of palivizumab are based on the belief that the risk of RSV hospitalization (RSVH) decreases significantly after 3 mo of age1or that, because of higher mean serum palivizumab levels after multiple doses, high-risk infants will maintain their protection for longer than a month following the last NGD-4715 dose.3 This review will discuss the evidence for monthly dosing of palivizumab throughout the RSV season from a pharmacokinetic perspective and NGD-4715 with regard to the risk of RSVH in high-risk infants by chronologic age during the season. == Historical Overview of Guidelines == In 2003, AAP NGD-4715 guidelines for RSV prophylaxis in high-risk infants recommended that infants requiring medical therapy due to chronic lung disease (CLD) or congenital heart disease (CHD) and preterm infants born 35 wk gestational age (wGA) receive 5 successive monthly doses of palivizumab to ensure continual coverage throughout the RSV season.4In 2009, the AAP guidelines were revised for preterm infants 3234 wGA to recommend dosing only through 90 d of age, with a maximum of 3 doses, regardless of when during the season the third dose was given.5These new recommendations were based on the rationale that once an infant has passed 90 days of age, the risk of hospitalization attributable to RSV lower respiratory tract disease is reduced.5 In Canada, the British Columbia Immunoprophylaxis Committee revised its guidelines for RSV prophylaxis in 2012 to state that all high-risk infants are eligible to receive a maximum of 4 doses of palivizumab; in 2013, the exception of qualifying children with certain cardiac conditions, who may receive a maximum of 5 doses, was added.2Preterm infants 2934 wGA are further restricted to a maximum of 3 doses because they are viewed as lower risk than preterm infants 28 wGA and infants with CLD or CHD. These variations in dosing appear to be driven by cost-reduction goals and supported by a retrospective literature review comprising preterm infants over a range of gestational ages.6This analysis reported that therapeutic levels of palivizumab result in protective trough CRYAA levels of 30 g/mL for 152171 d after the fourth dose and 120138 d after the third dose and that the calculated average half life for the first PVZ IM (palivizumab delivered intramuscularly -Ed.) dose ranged from 23 to 32 days but, by the fourth dose, the average half life increased to a range of 26 to 40 days.6 == Passive Vs. Active Immunity == Unlike a vaccine that induces long-lasting immunity, palivizumab is an exogenous antibody that degrades over time and needs to be replenished monthly to allow for continued protection against RSV.7Vaccines are recommended to be given to preterm infants at the same dose and same chronologic age as term infants.8Even though immunogenicity may be decreased, antibody concentrations usually remain protecting. Vaccine recommendations that are consistent for all babies (term or preterm) limit misunderstandings with healthcare companies and parents. The same reasoning for guideline consistency can be applied.
