AMERICAN ACADEMY OF PEDIATRICS Committee on Infectious Diseases and Committee on Fetus and Newborn Prevention of Respiratory Syncytial Virus Infections: Indications for the Use of Palivizumab and Update on the Use of RSV-IGIV ABSTRACT. The Food and Drug Administration re- rophylaxis to prevent respiratory syncytial vi- cently approved the use of palivizumab (pale¯-vizhu¯- rus (RSV) infection in infants and children at ma¨b), an intramuscularly administered monoclonal anti- increased risk for severe disease, particularly body preparation. Recommendations for its use are based P those with chronic lung disease (CLD) receiving med- on a large, randomized study demonstrating a 55% re- ical management on a long-term basis, is now available duction in the risk of hospitalization attributable to re- using either an intravenous or an intramuscular prep- spiratory syncytial virus (RSV) infections in high-risk pediatric patients. Infants and children with chronic lung aration. Choosing which product to use in individual disease (CLD), formerly designated bronchopulmonary patients will depend on age, availability of intravenous dysplasia, as well as prematurely born infants without access, cost, and other factors. Neither preparation is CLD experienced a reduced number of hospitalizations approved by the Food and Drug Administration (FDA) while receiving palivizumab compared with a placebo. for infants or children with congenital heart disease Both palivizumab and respiratory syncytial virus im- (CHD). Unlike respiratory syncytial virus immune mune globulin intravenous (RSV-IGIV) are available for globulin intravenous (RSV-IGIV), recipients of palivi- protecting high-risk children against serious complica- zumab do not require delaying measles-containing tions from RSV infections. Palivizumab is preferred for vaccine or varicella vaccine. most high-risk children because of ease of administra- tion (intramuscular), lack of interference with measles– mumps–rubella vaccine and varicella vaccine, and lack of BACKGROUND complications associated with intravenous administra- RSV-IGIV (RespiGam, Massachusetts Public Health tion of human immune globulin products. RSV-IGIV, Biologic Laboratories, and MedImmune, Inc, Gaithers- however, provides additional protection against other burg, MD) was licensed by the FDA in January 1996 for respiratory viral illnesses and may be preferred for prevention of severe RSV lower respiratory tract dis- selected high-risk children including those receiving ease in infants and children younger than 24 months replacement intravenous immune globulin because of with CLD or a history of premature birth (#35 weeks underlying immune deficiency or human immuno- of gestation). Recommendations for the use of this deficiency virus infection. For premature infants about to product have been summarized previously by the be discharged from hospitals during the RSV season, 1 physicians could consider administering RSV-IGIV for American Academy of Pediatrics (AAP). Randomized, the first month of prophylaxis. controlled clinical trials demonstrated the efficacy and Most of the guidelines from the American Academy of safety of monthly RSV-IGIV infusions in selected in- Pediatrics for the selection of infants and children to fants.2,3 Although RSV-IGIV was the first agent with receive RSV-prophylaxis remain unchanged. Palivi- demonstrated efficacy for prophylaxis against RSV in- zumab has been shown to provide benefit for infants fections, and did provide a 41% reduction in RSV hos- who were 32 to 35 weeks of gestation at birth. RSV-IGIV pitalizations, several disadvantages are associated with is contraindicated and palivizumab is not recommended this product. On the basis of available clinical trials, the for children with cyanotic congenital heart disease. The safety and efficacy of RSV-IGIV in children with CHD number of patients with adverse events judged to be related to palivizumab was similar to that of the placebo has not been established. Children with cyanotic CHD group (11% vs 10%, respectively); discontinuation of in- who received RSV-IGIV and underwent cardiac sur- jections for adverse events related to palivizumab was gery appeared to experience an increased surgical mor- rare. tality rate.4 RSV-IGIV prophylaxis requires monthly intravenous infusion throughout the RSV season, and like palivizumab is costly.5 Also, a widespread shortage ABBREVIATIONS. RSV, respiratory syncytial virus; CLD, chronic lung disease; FDA, Food and Drug Administration; CHD, congen- of RSV-IGIV during the past two winter seasons made ital heart disease; RSV-IGIV, respiratory syncytial virus immune supplies unreliable. The need for alternative ap- globulin intravenous; AAP, American Academy of Pediatrics; proaches to the prophylaxis of RSV infection in high- ICU, intensive care unit; MMR, measles–mumps–rubella; IPV, risk infants is apparent. inactivated poliovirus vaccine; OPV, oral poliovirus vaccine; IGIV, immune globulin intravenous. A recent study using a RSV intramuscular monoclo- nal antibody, palivizumab, (Synagis, MedImmune, Inc, Gaithersburg, MD) provided an alternative ap- proach to the prevention of RSV infections in high-risk The recommendations in this statement do not indicate an exclusive course infants. Palivizumab is a humanized monoclonal anti- of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. body directed against the F glycoprotein of RSV—a PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad- surface protein that is highly conserved among RSV emy of Pediatrics. isolates.6 Because the monoclonal antibody is not de- Downloaded from www.aappublications.org/newsPEDIATRICS by guest on October Vol. 1021, 2021 No. 5 November 1998 1211 rived from human immune globulin, it is free of poten- and RSV infection risk factors (ie, prematurity, neonatal tial contamination by infectious agents and can be pro- CLD). Prophylaxis resulted in a 55% overall reduction duced readily in batch lots; thus, shortages are not in RSV-related hospitalizations (11% to 5% in placebo anticipated. The recently completed IMpact-RSV clini- vs palivizumab recipients, respectively, P , .001). cal trial defines the usefulness of this product for pre- Small differences in rates of hospitalizations were vention of RSV disease in high-risk infants.7 Palivi- noted between placebo and prophylaxis groups in dif- zumab was approved by the FDA in June 1998 based ferent geographic regions. These rates were 10% pro- on the results of this trial. This statement summarizes phylaxis compared with 5% placebo for the United existing data on palivizumab and provides recommen- States, 15% prophylaxis compared with 9% placebo for dations concerning its appropriate use in clinical prac- Canada, and 10% prophylaxis compared with 4% pla- tice. Previous policy from the AAP has described other cebo for the United Kingdom. aspects of RSV disease: epidemiologic characteristics, The number of days of hospitalization for RSV infec- risk factors for serious illness, laboratory diagnosis, and tion per 100 children was decreased from 62 in patients treatment with ribavirin8 as well as use of RSV-IGIV.1 receiving a placebo to 36 in those receiving palivi- zumab (P , .001). Clinical benefit could be ascribed for CLINICAL STUDIES additional secondary endpoints (Table 1), including Clinical Efficacy of Palivizumab decreased requirement for supplemental oxygen, a de- During the winter of 1996 and 1997, 1502 infants crease in the number of days of moderate or severe were enrolled in a multicenter, double-blind, ran- lower respiratory tract illness per 100 children (illness domized clinical trial of palivizumab (2:1 enrollment, severity score), or a reduction in the requirement for treated vs placebo group). At 30-day intervals, start- hospitalization in an ICU. No statistically significant ing at the onset of the RSV season, 5 intramuscular differences were identified for the requirement of me- 7 doses (15 mg/kg) of either palivizumab or a placebo chanical ventilation or in the incidence of otitis media. were administered. Children eligible for participa- The mortality rate was low in both study populations. tion in the clinical trial were younger than 2 years Among placebo recipients, 5 children died (1%) com- with CLD who required continuing medical therapy pared with 4 children who received palivizumab (supplemental oxygen, bronchodilator, and diuretic (0.4%). Hospital deaths during the study occurred in 2 or corticosteroid therapy) and children 35 weeks of of the palivizumab recipients, 1 attributed to aspiration gestation or less who were younger than 6 months at and the other to complications of liquid ventilation in a the start of the RSV season. The primary endpoint child with RSV pneumonia. was efficacy of prophylaxis in reducing the incidence Adverse events were not significant. Overall, the of hospitalization for RSV infections. Secondary end- development of erythema, pain, and induration at points included the total number of hospital days the site of intramuscular injection resulted in adverse attributable to RSV as well as other respiratory vi- events in 2% of the placebo recipients and in 3% of 7 ruses, days of supplemental oxygen therapy, days of infants receiving palivizumab. There were no signif- altered respiratory illness score (the respiratory ill- icant differences in adverse event rates or the appear- 9 ness score included work of breathing, respiratory ance of antibody to