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Monthly doses of palivizumab, an RSV-specific monoclonal antibody, reduce RSV-related hospitalizations (RSVH) in high-risk children; however, no specific palivizumab level has been correlated with disease severity in humans. A post hoc analysis of a previous randomized, placebo-controlled trial evaluated the relationship between serum palivizumab level at the time of RSVH and disease severity. Pediatric intensive care unit (PICU) admission was the primary severity marker. Relationships were evaluated between disease severity and gestational age, age at enrollment, age at RSVH, presence of bronchopulmonary dysplasia, sex, race, multiple birth, household smoking, daycare attendance, sibling(s), family history of atopy, duration between most recent palivizumab dose and RSVH, and palivizumab level at RSVH. Forty-two (87.5%) of 48 palivizumab recipients with RSVH had palivizumab levels drawn; 11 were admitted to the PICU. Mean palivizumab levels were lower in PICU-admitted subjects (47.2 μg/mL) vs. non-PICU subjects (98.7 μg/mL; P < 0.0001); there were no statistically significant differences in other variables examined. The probability of PICU admission declined with higher palivizumab levels; there were no PICU admissions with levels ≥ 92 μg/mL. In multivariate analyses, palivizumab level was the only independent predictor of PICU admission (P = 0.009). Palivizumab level also correlated with duration of RSVH and PICU stay, supplemental oxygen use and duration, and mechanical ventilation use and duration (P < 0.05). Higher palivizumab level was associated with decreased disease severity in high-risk infants with RSVH. Findings suggest that palivizumab level has clinical relevance, and adherence to timely monthly dosing may confer additional protection among high-risk children receiving palivizumab.

Preterm infants ≤ 35 weeks' gestational age (GA), and children ≤ 24 months of age with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart disease (hsCHD) are at high risk for developing severe respiratory syncytial virus (RSV) disease. In 3 previous randomized, placebo-controlled trials, palivizumab efficacy varied significantly based on these underlying conditions, and trial enrollment was not proportional to condition prevalence. This analysis provides the first estimate of the population-weighted efficacy of palivizumab in high-risk children, adjusting for condition prevalence. Palivizumab efficacy by high-risk condition was obtained from the clinical trials. The annual number of US children with each condition was obtained from the 2010 Centers for Disease Control and Prevention (CDC) natality statistics and the medical literature. Data from specialty pharmacies in the US palivizumab distribution network were used to estimate the population for each condition receiving at least 1 dose in the outpatient setting in 2012-2013. The weighted efficacy estimate was derived by summing the products of the condition-specific relative risk reductions and the relative frequency of each condition among those receiving palivizumab. The US population-weighted efficacy estimate for those receiving palivizumab was 68%. Due to the low prevalence of BPD and hsCHD and the higher efficacy observed in preterm infants without BPD or CHD, the population-weighted estimate of palivizumab efficacy is higher than the overall 45-55% efficacy observed in initial clinical trials. Consistent with 2012 American Academy of Pediatrics RSV prophylaxis recommendations, a low proportion of preterm infants 32-35 weeks' gestational age receive palivizumab.