Lower respiratory illness that results from respiratory syncytial virus (RSV) infection has long been recognized as a serious health risk to infants and children with congenital heart disease (CHD).1,2 In particular, RSVtriggered pulmonary hypertension, complications in managing heart failure, and prolonged mechanical ventilatory assistance may all delay or jeopardize the successful cardiac surgical palliation or repair of these children. Many of the health concerns for these children mirror those for premature infants. Not surprisingly, the history of prevention of RSV disease in CHD infants and young children parallels that of premature infants with chronic lung disease.
Following an efficacy trial that included premature infants and children with CHD, hyperimmune RSV globulin (RSV-IGIV, RespiGam├óÔÇŞ╦İ MedImmune Inc., US) was approved by the US Food and Drug Administration (FDA) for the prevention of RSV lower respiratory illness in premature infants.3 Due to the small number of CHD patients and some safety concerns, a subsequent trial tested the safety and efficacy of RSV-IGIV in CHD patients specifically.4 This study failed to achieve its primary efficacy end-point of reduced RSV hospitalizations, although it did demonstrate the efficacy of this treatment in CHD patients below six months of age. There were significant safety concerns found in this study as there were an unexpectedly high number of surgically related adverse events in infants with cyanotic cardiac lesions. This was possibly due to altered blood viscosity in the treated patients.
Palivizumab (Synagis├óÔÇŞ╦İ MedImmune, Inc., US) is a monoclonal antibody (mAb) directed at the F surface glycoprotein of RSV that interrupts viral binding to cells in both RSV subtypes A and B. It was approved by the FDA for the prevention of RSV hospitalization in premature infants following an extensive multicenter clinical trial.5 Subsequently, in what remains the largest drug trial conducted in CHD patients, over four RSV seasons (1998├óÔé¼ÔÇ£2002) 1,287 CHD patients were randomized to a double-blind, placebo-controlled clinical trial powered to test the efficacy and safety of palivizumab.6 The primary efficacy end-point of reduced RSV hospitalizations was met (45% relative reduction in treated group) and, unlike RSV-IVIG, no serious safety concerns for palivizumab were observed, leading to the addition of infants and children <24 months of age with hemodynamically significant CHD to prophylaxis indications.7
- MacDonald NE, Hall CB, Suffin SC, et al., Respiratory syncytial viral infection in infants with congenital heart disease, N Engl J Med, 1985;307:397├óÔé¼ÔÇ£400.
- Altman CA, Englund JA, Demmler G, et al., Respiratory syncytial virus in patients with congenital heart disease: a contemporary look at epidemiology and success of pre-operative screening, Pediatr Cardiol, 2000;21:433├óÔé¼ÔÇ£8.
- The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis, Pediatrics, 1997;99:93├óÔé¼ÔÇ£9.
- Simoes EA, Sondheimer HM, Top FH Jr, et al., Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group, J Pediatr, 1998;133:492├óÔé¼ÔÇ£9.
- The Impact-RSV Study Group, Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants, Pediatrics, 1998;102:531├óÔé¼ÔÇ£7.
- Feltes TF, Cabalka AK, Meissner HC, et al., Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease, J Pediatr, 2003;143:532├óÔé¼ÔÇ£40.
- American Academy of Pediatrics 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├óÔé¼ÔÇ£6.
- Castelli JB, Maeda WT, Aiello VD, Respiratory syncytial virus as a trigger of a pulmonary hypertensive crisis after operative correction of aortic coarctation, Cardiol Young, 2007; in press.
- Tulloh RMR, Feltes TF, The European forum for clinical management: prophylaxis against the respiratory syncytial in infants and young children with congenital heart disease, Cardiol Young, 2005;15:274├óÔé¼ÔÇ£8.
- Nakazawa M, Saji T, Ichida F, et al., Guidelines for the use of palivizumab in infants and young children with congenital heart disease, Pediatrics Int, 2006;48:190├óÔé¼ÔÇ£93.
- Tulloh RM, Marsh M, Blackburn M, et al., Recommendations for the use of palivizumab as prophylaxis against respiratory syncytial virus in infants with congenital cardiac disease, Cardiol Young, 2003;13:420├óÔé¼ÔÇ£23.
- Su─é╦çrez Cabrera P, Malo Concepci─é┼én P, Maroto E, et al., Recomendaciones de la Sociedad Espa─é┬▒ola de Cardiolog─é┬¡a Pedi─é╦çtrica y Cardiopat─é┬¡as Cong─é┬®nitas para la prevenci─é┼én de la infecci─é┼én por virus respiratorio sincitial en pacientes con cardiopat─é┬¡a cong─é┬®nita, 2004; available at: http://www. secardioped.org/
- Canadian National Advisory Committee on Immunization, Statement on the recommended use of monoclonal anti-RSV antibody (palivizumab), Can Commun Dis Rep, 2003;29:1├óÔé¼ÔÇ£15.
- Fuller H, Del Mar C, Immunoglobulin treatment for respiratory syncytial virus infection, Cochrane Database Syst Rev, 200618;(4): CD004883.
- Malley R, DeVincenzo J, Romilo O, et al., Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein, J Infect Dis, 1998;178:1555├óÔé¼ÔÇ£61.
- Saez-Llorens X, Moreno MT, Ramilo O, et al., Safety and pharmacokinetics of palivizumab therapy in children hospitalized with respiratory syncytial virus infection, Pediatr Infect Dis J, 2004;23:707├óÔé¼ÔÇ£12.
- Afghani B, Ngo T, Leu S-Y, et al., The effect of an interventional program of adherence to the American Academy of Pediatrics guidelines for palivizumab prophylaxis, Pediatr Inf Dis J, 2006;25:1019├óÔé¼ÔÇ£24.
- Mitchell I, Tough S, Gillis L, Majaesic C, Beyond randomized controlled trials: a ├óÔé¼´åİreal life™ experience of respiratory syncytial virus infection prevention in infancy with and without palivizumab, Pediatr Pulmonol, 2006;41(12):1167├óÔé¼ÔÇ£74.
- Meberg A, Bruu A-L, Respiratory syncytial virus infections in congenital heart defects ├óÔé¼ÔÇ£ hospitalizations and costs, Acta Paediatrica, 2006;95:404├óÔé¼ÔÇ£6.
- Duppenthaler A, Ammann RA, Gorgievski-Hrisoho M, et al., Low incidence of respiratory syncytial virus hospitalizations in haemodynamically significant congenital heart disease, Arch Dis Child, 2004;89:961├óÔé¼ÔÇ£5.
- Feltes TF, Simoes E, Letter to the Editor: Palivizumab prophylaxis in haemodynamically significant congenital heart disease, Arch Dis Child, 2005(8):875├óÔé¼ÔÇ£7.
- Yount LE, Mahle WT, Economic analysis of palivizumab in infants with congenital heart disease, Peds, 2004;114:1606├óÔé¼ÔÇ£11.
- Nuijten MJC,Wittenberg W, Lebmeir M, Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children, Parmacoeconomics, 2007;25:55├óÔé¼ÔÇ£71.
- Ashburn CA, McCrindle BW, Tchervenkov CI, et al., Outcomes after the Norwood operation in neonates with critical aortic stenosis and aortic valve atresia, J Thorac Cardiovasc Surg, 2003;125:1070├óÔé¼ÔÇ£82.
- Wu J, Pfarr DS, Johnson S, et al., Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract, J Mol Biol, 2007;20:[Epub].
- MedImmune.com website, Press Release, available at: http://phx.corporate-ir.net/phoenix.zhtml?c=83037&p=irolnewsArticle_ print&ID=638546