Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Abstract

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book. Pediatrics 2014;134:415-420 Policy statements from the American Academy of Pediatrics (AAP) are designed to provide updated guidance for child health care topics, with an emphasis on evidence-based recommendations whenever possible. Policy statements are reviewed at least every 3 years and updated when appropriate. In following this procedure, the AAP Committee on Infectious Diseases (COID) has undertaken a systematic review of all recent and older peer-reviewed literature relating to the burden of respiratory syncytial virus (RSV) disease in infants and children, focusing on publications that delineate children at greatest risk of serious RSV disease and studies that define pharmacokinetics, safety, and efficacy. Detailed input regarding this guidance has been solicited from 21 committees, councils, sections, and advisory groups within the AAP, as well as organizations outside the AAP. Outside groups include the

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“…For example, the recommended dose of palivizumab, a commercially available monoclonal antibody against respiratory syncytial virus infection in infants and young children, is 15 mg/kg once a month for 5 months (25). This means that 375 mg of the MAb is necessary to treat one 5-kg child.…”

Progress toward a Respiratory Syncytial Virus Vaccine

“…An alternative and promising approach to safeguard against severe RSV disease in early infancy is vaccinating pregnant women. Both monoclonal and polyclonal RSV antibodies delivered prophylactically to children clearly reduce the incidence of severe RSV disease and document the impact of antibody to RSV on disease prevention (2). In healthy populations, RSVspecific IgG transfer from pregnant women to infants is an active process resulting in higher antibody titers in the infant than in the mother (8).…”

“…No RSV vaccine is licensed anywhere in the world. While prophylactic treatment with RSV-specific neutralizing antibody is effective in reducing RSV morbidity in infants, its use is currently limited to select populations in high-resource settings because of its expense and because of challenges with its delivery (2). Prevention of severe RSV disease through active immunization of infants would be optimal but has been extremely challenging to implement, given the young age by which immunity is necessary and the legacy of vaccine-enhanced illness leading to deaths in a number of young children after receipt of a formalin-inactivated RSV vaccine in the 1960s.…”

Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs

“…, 27 For the prevention of RSV-infections, palivizumab administration is only recommended for high risk-infants 8 . The development of new approaches and therapeutic modalities are thus needed.…”