RESPIRATORY HOSPITALIZATIONS ASSOCIATED WITH PALIVIZUMAB COMPLIANCE IN THE CANADIAN REGISTRY OF SYNAGIS (CARESS)

Purpose: Palivizumab is used for respiratory syncytial virus (RSV) prophylaxis in high risk children, during the RSV season.  The purpose of the present study is to evaluate the current management (utilization, compliance) of children at high-risk of RSV infection with palivizumab prophylaxis in tertiary care centers and community settings using a Canadian Registry Database.

Method: A prospective, observational, registry of infants who received at least 1 dose of palivizumab during the 2005-2009 RSV seasons from 27 sites. Neonatal and demographic data were collected from the parent/caregiver at enrollment. Data on palivizumab utilization, compliance, and outcomes related to respiratory tract illness (RTI) were collected monthly.  Compliance was based on the number of days between injections.  RSV clinics currently administer approximately 5 monthly injections of palivizumab at 30 ± 5 day intervals, based on pharmacokinetic evidence from randomized controlled trials. However, an interval of 20 ± 4 days between the first and second injections, likely results in higher trough levels after the first dose, offering better protection against the virus.  Therefore, an interval of 16-35 days between the first and second injection was considered compliant, while intervals between subsequent doses were targeted for 25-35 days.

Result: 5286 infants aged 2 days to 47 months (mean=5.4 months) were enrolled. Participants were typically male (56.6%), Caucasian (71.7%) with an average gestational age (GA) of 32.2 ± 4.6 completed weeks. Only 7.0% of patients withdrew from the study.  No drug-related serious adverse events occurred.  308 infants had a total of 366 hospitalizations for RTI resulting in a hospitalization rate of 5.8%. The overall RSV positive hospitalization rate was 1.38%.  3766 infants (71.2%) were considered compliant with their treatment.  Non-compliant infants were more likely to be hospitalized for RTIs (6.9% vs. 5.4%, p = 0.038).  However, there were no significant differences in RSV-positive hospitalizations (p = 0.326).  Non-compliant infants were also more likely to have a mother that smoked (15.8% vs. 13.5%, p = 0.033) and had previously been prophylaxed with palivizumab (25.6% vs. 22.5%, p = 0.019).

Conclusion: 71.2% of infants were compliant with dosing recommendations.  Compliance was significantly associated with a lower likelihood of RTI hospitalization, but was not associated with RSV-positive hospitalizations. This may be due to the relatively small proportion of infants that were hospitalized with RSV.