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Can Fam Physician. 2010 October; 56(10): 988–991.
PMCID: PMC2954075

Rebuttal: palivizumab for the prevention of respiratory syncytial virus infection

Kelly A. Smart and Krista L. Lanctôt, PhD
Toronto, Ont
Bosco A. Paes, MB BS FRCPI FRCPC

In the article on palivizumab for the prevention of respiratory syncytial virus infection,1 Rogovik et al summarized current literature on palivizumab safety, efficacy, use, and cost-effectiveness. The primary objectives were to determine the indications for the use of palivizumab and whether it can be used in the treatment of respiratory syncytial virus (RSV) infections.

Although the recommendations for palivizumab use from the Canadian Paediatric Society2 are summarized, the discussion largely focuses on recommendations by the American Academy of Pediatrics,3 which is disappointing given the substantial research contributions to this field by the Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) and other Canadian investigators. As mentioned in the Canadian guidelines, there are important differences between the 2 position statements owing to unique epidemiology, geography, and practice settings, in addition to different health care systems and drug costs. Recommendations for infants at a gestational age (GA) of 32 to 35 weeks are the most divergent, with Canadian guidelines recommending localized policies in each province and territory, considering risk factors and the available risk-scoring tool.4,5 These recommendations are omitted from the authors’ summary table, and the differences between Canadian and American indications and rationale for the use of palivizumab in this specific subpopulation are not discussed. This is important, as this cohort of infants are at a risk similar to that of infants with a GA of less than 32 weeks with respect to RSV hospitalization rates, incurred morbidities during their hospital stays, and subsequent health care resource use.610 Moreover, the authors quote the use of 1 risk factor and a maximum of 3 doses for infants with a GA of 32 to 35 weeks born 3 months before or during the RSV season. There is ample evidence that more than 1 risk factor determines RSV hospitalization in this group of infants4,1113; further, the use of 1 to 3 doses of palivizumab during an entire RSV season is a strategy untested in randomized controlled trials14,15 and that is not supported by the pharmacokinetics and therapeutic efficacy of the drug, as evidenced in the earlier phase 1 and 2 and IMpact trials.14,16

The authors include a brief overview of palivizumab cost-effectiveness analyses. However, their survey of the literature is limited to only 1 paper, a UK-specific analysis,17 which is discussed in detail. Analyses of the cost-effectiveness of palivizumab might have limited generalizability among countries, as health care costs and cost-effectiveness standards can differ.18 None of the available Canadian analyses1922 is included in the discussion of cost-effectiveness or risk factors. Additionally, the variation in results and indications, even among the analyses cited, is not addressed. For example, Nuijten et al concluded that palivizumab is cost-effective for preterm infants and those with bronchopulmonary dysplasia or chronic heart disease,23 while Reeve et al only examined a group of infants of low birth weight and concluded that it was not cost-effective.24 A recent comprehensive review of the literature demonstrated that although results vary among countries and indications, palivizumab is often cost-effective for use in high-risk populations, especially those with multiple environmental risk factors.22

Furthermore, a big issue in Canada, which merits further attention, is the use of palivizumab in aboriginal populations. Palivizumab has been shown to be cost-effective for term Inuit infants in remote Northern communities21 owing to especially high rates of RSV infection and hospitalization costs.20 The number needed to treat in the Nunavut settlements of Igloolik, Arctic Bay, Grise Fjord, and Hall Beach20 varied from 2.5 to 3.7, unlike that of the IMpact randomized controlled trial. The Canadian Paediatric Society has also recognized the need for research in remote First Nations and Métis communities.2 Although Inuit infants are included in the summary of usage guidelines, the authors do not discuss aboriginal infants in the text or mention the important possible risks of RSV infection in this population.

In summary, the information in this article is incomplete and key Canadian references have been excluded. A comprehensive overview of the indications for which palivizumab is effective and cost-effective that includes Canadian data and focuses on guidelines published by the Canadian Paediatric Society for our urban and rural populations would be far more beneficial and informative for family physicians.

References

1. Rogovik AL, Carleton B, Solimano A, Goldman R. Palivizumab for the prevention or respiratory syncytial virus infection. Can Fam Physician. 2010;56:769–72. [PMC free article] [PubMed]
2. Samson L. Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Prevention of respiratory syncytial virus infection. Paediatr Child Health. 2009;14(8):521–32. [PMC free article] [PubMed]
3. Committee on Infectious Diseases From the American Academy of Pediatrics: policy statements—modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124(6):1694–701. Epub 2009 Sep 7. [PubMed]
4. Sampalis J, Langley J, Carbonell-Estrany X, Paes B, O’Brien K, Allen U, et al. Development and validation of a risk scoring tool to predict respiratory syncytial virus hospitalization in premature infants born at 33 through 35 completed weeks of gestation. Med Decis Making. 2008;28(4):471–80. Epub 2008 Jun 12. [PubMed]
5. Paes B, Steele S, Janes M, Pinelli J. Risk-scoring tool for respiratory syncytial virus prophylaxis in premature infants born at 33–35 completed weeks’ gestational age in Canada. Curr Med Res Opin. 2009;25(7):1585–91. [PubMed]
6. Boyce TG, Mellen BG, Mitchel EF, Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr. 2000;137(6):865–70. [PubMed]
7. Law B, Macdonald N, Langley J, Mitchell I, Stephens D, Wang E, et al. Severe respiratory syncytial virus infection among otherwise healthy prematurely born infants: what are we trying to prevent? Paediatr Child Health. 1998;3(6):402–4. [PMC free article] [PubMed]
8. Horn SD, Smout RJ. Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr. 2003;143(5 Suppl):S133–41. [PubMed]
9. Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr. 2003;143(5 Suppl):S142–9. [PubMed]
10. Sampalis J. Morbidity and mortality after RSV-associated hospitalizations among premature Canadian infants. J Pediatr. 2003;143(5 Suppl):S150–6. [PubMed]
11. Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I, et al. The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J. 2004;23(9):806–14. [PubMed]
12. Figueras-Aloy J, Carbonell-Estrany X, Quero-Jiménez J, Fernández-Colomer B, Guzmán-Cabañas J, Echaniz-Urcelay I, et al. FLIP-2 study: risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks. Pediatr Infect Dis J. 2008;27(9):788–93. [PubMed]
13. Carbonell-Estrany X, Figueras-Aloy J, Law BJ, Infección Respiratoria Infantil por Virus Respiratorio Sincitial Study Group. Pediatric Investigators Collaborative Network on Infections in Canada Study Group Identifying risk factors for severe respiratory syncytial virus among infants born after 33 through 35 completed weeks of gestation: different methodologies yield consistent finding. Pediatr Infect Dis J. 2004;23(11 Suppl):S193–201. [PubMed]
14. IMpact-RSV Study Group Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from syncytial virus infection in high-risk infants. Pediatrics. 1998;102(3 Pt 1):531–7. [PubMed]
15. Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH, Jr, et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr. 2003;143(4):532–40. [PubMed]
16. Sáez-Llorens X, Castaño E, Null D, Steichen J, Sánchez PJ, Ramilo O, et al. Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group. Pediatr Infect Dis J. 1998;17(9):787–91. [PubMed]
17. Wang D, Cummins C, Bayliss S, Sandercock J, Burls A. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation. Health Technol Assess. 2008;12(36):iii, ix–x, 1–86. [PubMed]
18. Morris SK, Dzolganovski B, Beyene J, Sung L. A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection. BMC Infect Dis. 2009;9:106. [PMC free article] [PubMed]
19. Lanctôt KL, Masoud ST, Paes BA, Tarride JE, Chiu A, Hui C, et al. The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32–35 weeks: a Canadian-based analysis. Curr Med Res Opin. 2008 Oct 16; Epub ahead of print. [PubMed]
20. Banerji A, Lanctôt KL, Paes BA, Masoud ST, Tam DY, Macdonald WA, et al. Comparison of the cost of hospitalization for respiratory syncytial virus disease versus palivizumab prophylaxis in Canadian Inuit infants. Pediatr Infect Dis J. 2009;28(8):702–6. [PubMed]
21. Tam DY, Banerji A, Paes BA, Hui C, Tarride JE, Lanctôt KL. The cost-effectiveness of palivizumab for term Inuit infants in the Eastern Canadian Arctic. J Med Econ. 2009;12(4):361–70. [PubMed]
22. Smart KA, Lanctôt KL, Paes BA. The cost-effectiveness of palivizumab: a systematic review of the evidence. J Med Econ. 2010 Jul 23; Epub ahead of print. [PubMed]
23. Nuijten MJC, Wittenberg W, Lebmeier M. Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis. Pharmacoeconomics. 2007;25(1):55–71. [PubMed]
24. Reeve CA, Whitehall JS, Buettner PG, Norton R, Reeve DM, Francis F. Cost-effectiveness of respiratory syncytial virus prophylaxis with palivizumab. J Paediatr Child Health. 2006;429(5):253–8. [PubMed]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada