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Important recommendations for palivizumab usage included in revised Red Book
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The 28th edition of the Red Book, the Report of the Committee on Infectious Diseases (COID), has recently been released. It would not be an exaggeration to state that few other reference resources may be as widely used or as trusted as the Red Book. Each edition of the Red Book is updated by members of the COID to provide the most current information; resulting in a succinct, up-to-date reference that can be rapidly searched to obtain the desired information. The 28th edition of the Red Book follows in the tradition of its predecessors with new chapters added, others merged into existing ones and several undergoing extensive or significant updates.
The chapter dealing with respiratory syncytial virus (RSV) is such a chapter (2009: 562-568.) Updated information regarding epidemiology, diagnostic testing, management of RSV-infected children and infection-control measures are provided. In addition, the chapter contains an extensive revision of the recommendations for the use of palivizumab in high-risk infants.
Palivizumab was approved by the FDA for prevention of serious lower respiratory tract disease in high-risk infants (≤35 weeks gestation or chronic lung disease) in 1998. Results of the randomized clinical trial used to obtain FDA approval were published that same year. Inclusion criteria were a gestational age of ≤35 weeks and a postnatal age of ≤6 months or a postnatal age of ≤24 months with a diagnosis of bronchopulmonary dysplasia requiring ongoing medical treatment.
Infants received palivizumab every 30 days for five doses. Prophylaxis reduced RSV hospitalizations by 55%. For infants 32 weeks through 35 weeks gestational age, the reduction in hospitalization was approximately 80%. A subsequent trial conducted between 1998 and 2002 documented the efficacy of palivizumab for the prevention of serious RSV infection in infants and children with hemodynamically significant congenital heart disease (CHD).
Guidelines for the use of palivizumab were first published in 1997 and were based on inclusion criteria used in the phase 3 registration trial. Because of the cost of palivizumab and the large number of premature infants born between 32 to 35 weeks gestation, risk factors as selection criteria were added to this group. A revision of the recommendations for immunoprophylaxis of RSV was issued in 2003 that included refinement of the risk factors and the need for two of the latter in the 32 to 35 weeks gestational age group.
The current Red Book recommendations contain no modifications in palivizumab eligibility criteria for infants with chronic lung disease of prematurity, hemodynamically significant congenital heart disease or infants with gestational age of ≤32 weeks form those published in 2006. Infants born before 35 weeks of gestation with congenital abnormalities of the airway or a neuromuscular condition that compromises handling of respiratory secretions remain eligible for immunoprophylaxis.
Recommendations for the timing of the initiation of immunoprophylaxis have been modified to reflect the current knowledge of RSV seasonality reported by the CDC. Regardless of the month when immunoprophylaxis is initiated, a recommendation is made for a maximum five doses of palivizumab for infants with the conditions indicated above.
Recommendation changes
Major changes in the recommendations for immunoprophylaxis of infants with a gestational age between 32 weeks and 35 weeks are contained in the current COID report.
Eligibility for this gestational age group has been modified to include only those infants younger than 3 months of age (previously 6 months) at the onset of RSV season or those born during RSV season and one of two risk factors (child care attendance or sibling <5 years of age). Previous guidelines required that infants have two of five risk factors (child care attendance, school-aged siblings, exposure to environmental pollutants, congenital airway abnormalities or severe neuromuscular disease). Infants meeting these criteria are limited as to the number of doses of palivizumab that they may receive. Infants may receive immunoprophylaxis until 3 months of age and should not receive more than three doses.
It is not surprising that the significant changes listed above for immunoprophylaxis in the 32 week to 35 week gestational age group have raised curiosity as the body of literature is reviewed to arrive at the current recommendations. Additionally, the timing of the release of the report coincided with the time that many states and health care organizations define eligibility criteria for RSV immunoprophylaxis. In arriving at eligibility criteria for RSV immunoprophylaxis, many states and health care organizations rely on pediatricians to advise them as to appropriateness of the suggested criteria. An understanding of the literature used to arrive at the current recommendations is essential to providing sound recommendations to these agencies.
A summary of changes from the previous policy statement was posted in the members section of the AAP website (http://www.aap.org/moc/docs/ 070209rsv.cfm) in early July but did not contain references reviewed by the COID in arriving at the current recommendations. In late August, a posting of the reference list from the RSV policy statement was placed on the website (http://www.aap.org/moc/docs/070209ebreaking.cfm.) While these citations provide the rationale for some of the changes contained in the COID report, they do not fully address all of the major changes recommended.
If informed decisions are to be made, a clear understanding of the issues is essential. If adopted, the COID recommendations will have a significant impact on RSV prophylaxis in the United States. When issuing recommendations of this significance, the COID may wish to consider simultaneous release of a policy statement containing those citations reviewed by the committee in arriving at its conclusions. This information will help those advising states and health care organizations in assessing the appropriateness of their recommendations.
Jose Romero, MD, FAAP, is Professor of Pediatrics and Chief, Pediatric Infectious Diseases Section at Arkansas Children’s Hospital/University of Arkansas for Medical Sciences and Director, Clinical Trials Research at Arkansas Children’s Hospital Research Institute.
For more information:
- The Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody reduces hospitalization from respiratory syncytial virus in high-risk infants. Pediatrics. 1998;102:531-537.
- Feltes TF, et al. Cardiac Synagis Study Group. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr. 2003;143: 532-540.
- COID and Committee on Fetus and Newborn. Prevention of RSV: Indications for the Use of palivizumab and update on the use of RSV-IGIV. Pediatrics. 1998;102: 1211-1216.
- AAP Committee on Infectious Diseases and Committee on Fetus and Newborn. Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics. 2003;112: 1442-1446.