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PEDIATRICS Vol. 102 No. 3 September 1998, pp. 531-537
Received Feb 20, 1998; accepted Jun 3, 1998.
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 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 a 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. Key words: respiratory syncytial virus, monoclonal antibody, prophylaxis, MEDI-493, palivizumab, Synagis, prematurity, bronchopulmonary dysplasia.
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