Synagis Efficacy & Safety

Objective: To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.

Methods: A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (≤35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for a total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and ~93% received all five scheduled injections.

Results: Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.

Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD Pediatrics 1998;102:531-537.

Objective: To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).

Study design: A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.

Results: Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P = .003), a 56% reduction in total days of RSV hospitalization per 100 children (P = .003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P = .014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P < .005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.

Conclusions: Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD. (J. Pediatr 2003;143:532-40)

Objective: To assess airway function at 1 year and compare this with similar measurements made shortly after birth in preterm infants without clinical neonatal respiratory disease.

Study design: Infants born at ≤36 weeks' gestational age were eligible if they required no neonatal ventilatory support and were otherwise healthy. Paired measurements of maximal expiratory flow at functional residual capacity (V'maxFRC) were obtained ~3 weeks after birth in 24 preterm infants (gestational age [mean ± SD], 33.2 ± 2.2 weeks) and repeated at a corrected postnatal age (mean ± SD) of 57.0 ± 12.2 weeks. V'maxFRC values were expressed as Z scores by means of sex-specific prediction equations.

Results: V'maxFRC was within normal range for all infants shortly after birth (mean ± SD Z score: -0.06 ± 0.92). By 1 year, Z scores had reduced significantly [mean (95% CI) 2nd-1st test: -1.94 (-2.27, -1.60)]. V'maxFRC Z scores at 3 weeks were highly correlated with those at 1 year of age (Spearman correlation coefficient 0.64).

Conclusions: Airway function during the first year shows considerable tracking. Even in the absence of neonatal respiratory disease, preterm delivery is associated with altered airway development during early infancy. (J Pediatr 2002;141:652-8)

Objectives: To determine if gestational age (GA) is independently associated with hospital resource use and outcomes among infants hospitalized for respiratory syncytial virus (RSV).

Study design: Analysis of retrospective data from 304 infants (≤1 year) with bronchiolitis or RSV pneumonia admitted to nine children's hospitals from April 1995 to September 1996. Resource use and outcomes examined included admission to the intensive care unit (ICU), intubation, and hospital and ICU length of stay. The Comprehensive Severity Index controlled for severity of illness.

Results: Two hundred fifteen term infants (GA ≥37 weeks) and 89 infants with GA <37 weeks, divided according to GA into 3 subgroups: (≤32, 33 to 35, and 36 weeks), were compared. Significant differences were found for rate of intubation (P = .002) and ICU and hospital length of stay (P = .021 and P < .0001, respectively), with the highest resource use in 33 to 35 weeks GA infants, which remained significant in multiple regression analyses.

Conclusions: Infants 33 to 35 weeks GA had hospital outcomes that were negative or worse than infants ≤32 weeks GA. Data suggest prematurity ≤35 weeks GA significantly increases the risk for severe outcomes among infants hospitalized for RSV. Infants 36 weeks GA had outcomes similar to term infants. No evidence was observed of gradation or inverse linear risk relation between GA and hospital outcomes. (J. Pediatr 2003;143:S133-S141)

Background: The recent number and rate of infant hospitalizations with a respiratory syncytial virus (RSV)-coded diagnosis have not been published.

Methods: Retrospective data analysis. National Hospital Discharge Survey data for 1997 to 1999 were analyzed for discharges of infants <1 year old with an RSV-coded diagnosis (ICD-9-CM 466.11, 480.1, 079.6). Hospitalization rates were estimated with annual midyear Census data.

Results: RSV bronchiolitis was the leading primary diagnosis annually for all infants hospitalized for any reason. Between 1997 and 1999, 297 684 RSV-coded discharges of infants with an RSV-coded diagnosis occurred. The associated hospitalization rate was 25.2 per 1000 infants. RSV-coded discharges peaked in February.

Conclusion: RSV bronchiolitis was the leading cause of hospital admissions of infants younger than age 1 year for any reason between 1997 and 1999.