Palivizumab: RSV prophylaxis

• Palivizumab, a humanized murine monoclonal immunoglobulin
• Standard dosing is 15 mg/kg administered intramuscularly every 30 days during RSV season for a maximum of five doses
  

Efficacy

• results of randomized controlled trials (RCTs) investigating palivizumab, demonstrating a reduction in hospitalizations of approximately
• 80% in infants with prematurity but without chronic lung disease of prematurity (CLD)
• 40% in infants with CLD
• 45% in children with congenital heart disease (CHD)
• Efficacy was not demonstrated in the CHD subgroup with cyanotic heart disease
• A recent systematic review summarized 20 published observational palivizumab studies and estimates of effectiveness were generally in the range predicted by the RCTs

Cost-Effectiveness

• Reports concerning the cost-effectiveness of palivizumab have varied, owing in large part to disparate estimates of its short- and long-term benefit
• Short-term benefits- there is no evidence that palivizumab prevents mechanical ventilation or death or that breakthrough RSV hospitalizations are less severe than hospitalizations in control
• Long term benefits - one RCT showed that palivizumab administered to infants 33 to 35 weeks’ GA without CLD decreased days with parent-reported wheezing in the first year from 4.5% to 1.8% (P<0.001; number needed to treat = 38) and decreased recurrent wheezing from 21% to 11% (P=0.01)
• Palivizumab prophylaxis has limited effect on RSV hospitalizations on a population basis, no measurable effect on mortality, and a minimal effect on subsequent wheezing
• technical review for the 2014 updated American Academy of Pediatrics (AAP) guidance for palivizumab prophylaxis indicates that palivizumab "cannot be considered as high-value health care for any group of infants" because its high cost is associated with minimal benefit
• Prophylaxis must be provided to many infants to prevent one hospitalization while the cost to provide prophylaxis to a single infant (approximately $5,600) exceeds that of a typical RSV hospitalization (three or four days).

Recommended Use

High Risk	Defination	Recommendation
hemodynamically significant CHD or CLD	need for oxygen at 36 weeks’ GA, who require ongoing diuretics, bronchodilators, steroids or supplemental oxygen	·         should receive palivizumab if they are <12 months of age at the start of RSV season. ·         not indicated during the second RSV season for infants with CHD ·         not indicated for majority of children with CLD (with the exception of those still on or weaned off of supplemental oxygen in the past three months)
preterm infants without CLD	born before 30 + 0 weeks’ GA who are <6 months of age at the start of RSV season	·         reasonable (but not essential) to offer palivizumab ·         Infants born after 30 + 0 weeks’ GA have RSV admission rates that are consistently ≤7% (90 doses of palivizumab to prevent one RSV admission) ·         not recommended in the second year of life on the basis of a history of prematurity alone
preterm infants with CLD	gestational age <32 weeks, 0 days and a requirement for >21% oxygen for at least the first 28 days after birth	·         Prophylaxis may be considered during the RSV season during the first year of life
immunodeficiencies, Down syndrome, cystic fibrosis, upper airway obstruction or a chronic pulmonary disease other than CLD		·         should not routinely be offered palivizumab However, prophylaxis may be considered for children <24 months of age who are on home oxygen, have had a prolonged hospitalization for severe pulmonary disease or are severely immunocompromised
pulmonary abnormality or neuromuscular disease	disease that impairs the ability to clear secretions from the upper airways	·         No prospective studies or populationbased data are availabl ·         may be considered for prophylaxis during the first year of life (due to risk for a prolonged hospitalization related to lower respiratory tract infection)
health care-associated RSV	prevention	·         not recommended
breakthrough RSV infection	breakthrough RSV infection during monthly palivizumab	·         Continuation of monthly palivizumab is not recommended ·         Repeat RSV infections in one season are not common

Recommendation

• Good hand hygiene in the home and avoiding contact of high-risk children with people with RTIs, where practical, remain paramount for RSV prevention.
• Breastfeeding and avoidance of exposure to cigarette smoke should be encouraged.
• Given that the efficacy of palivizumab is <50% in the highest-risk groups (CLD or CHD), and that most hospitalizations occur in healthy term infants, more education should be directed at such prevention strategies
• Based on lack of evidence that palivizumab prevents severe outcomes, palivizumab is unlikely to be cost-effective in children with prematurity, CLD or CHD, and can only be potentially cost-effective in settings where RSV hospitalizations are exceedingly common and very expensive

References:

1. www.uptodate.com
2. www.bestpractice.BMJ.com
3. Preventing hospitalizations for respiratory syncytial virus infection. Canadian Paediatric Society Infectious Diseases and Immunization Committee Paediatr Child Health 2015;20(6):321-26. Updated: May 12 2016
4. Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection. PEDIATRICS Volume 134, Number 2, August 2014.
5. Cost-effectiveness of palivizumab compared to no prophylaxis in term infants residing in the Canadian Arctic. cmajo October 18, 2016 vol. 4 no. 4 E623-E633
6. A cost-effectiveness analysis of respiratory syncytial virus (RSV) prophylaxis in infants in the United Kingdom. Health Economics Review20133:18