Download PDF
CC BY-NC-ND 4.0 · Am J Perinatol 2022; 39(15): 1668-1677
DOI: 10.1055/s-0041-1725146
Original Article

Respiratory Syncytial Virus Immunoprophylaxis with Palivizumab: 12-Year Observational Study of Usage and Outcomes in Canada

Ian Mitchell 
1   Department of Paediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada
,
Abby Li
2   Medical Outcomes and Research in Economics, Sunnybrook Health Sciences, Centre, Toronto, Ontario, Canada
,
Candice L. Bjornson
1   Department of Paediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Alberta, Canada
,
Krista L. Lanctot
2   Medical Outcomes and Research in Economics, Sunnybrook Health Sciences, Centre, Toronto, Ontario, Canada
,
Bosco A. Paes 
3   Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
,
the CARESS investigators › Author Affiliations Funding The Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab (CARESS) is funded by an investigator-initiated grant from AbbVie Corporation (A05-130).
› Further Information
Also available at
   Permissions and Reprints

Abstract

Objective This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH).

Study Design It involves a large, Canadian prospective (2005–2017) observational multicenter study of children at high risk for RSV infection.

Results A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); “miscellaneous” (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The “miscellaneous” group increased over time (4.4% in 2005–2006 to 22.5% in 2016–2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual “unclassified” group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4–18.2; p < 0.0005) more likely to have RSVH than infants without risk factors. Three adverse events occurred; none were fatal.

Conclusion Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required.

Key Points

  • Main indications were prematurity (63.3%); “miscellaneous” (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%).

  • The proportion of children in the “miscellaneous” group, comprised of those with trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual “unclassified” group, increased over time (4.4% in 2005–2006 to 22.5% in 2016–2017).

  • Respiratory illness-related hospitalization occurred in 2,054 children (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH: 1.6%).

Keywords

RSV infection - palivizumab - prematurity - bronchopulmonary dysplasia - chronic lung disease - hemodynamically significant congenital heart disease - children with medical complexity

Registration

ClinicalTrials.gov Identifier: NCT00420966.




Publication History

Received: 10 July 2020

Accepted: 19 January 2021

Article published online:
03 March 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus—a comprehensive review. Clin Rev Allergy Immunol 2013; 45 (03) 331-379
    CrossrefPubMedSearch in Google Scholar
  • 2 Higgins D, Trujillo C, Keech C. Advances in RSV vaccine research and development—a global agenda. Vaccine 2016; 34 (26) 2870-2875
    CrossrefPubMedSearch in Google Scholar
  • 3 Resch B. Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection. Hum Vaccin Immunother 2017; 13 (09) 2138-2149
    CrossrefPubMedSearch in Google Scholar
  • 4 Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102 (3, pt. 1): 531-537
    Search in Google Scholar
  • 5 Feltes TF, Cabalka AK, Meissner HC. 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 (04) 532-540
    CrossrefPubMedSearch in Google Scholar
  • 6 Robinson JL, Le Saux N. Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Preventing hospitalizations for respiratory syncytial virus infection. Paediatr Child Health 2015; 20 (06) 321-333
    CrossrefPubMedSearch in Google Scholar
  • 7 Mitchell I, Paes BA, Li A, Lanctôt KL. CARESS investigators. CARESS: the Canadian registry of palivizumab. Pediatr Infect Dis J 2011; 30 (08) 651-655
    CrossrefPubMedSearch in Google Scholar
  • 8 Paes B, Mitchell I, Li A, Harimoto T, Lanctôt KL. Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005-2012) compared to other international registries. Clin Dev Immunol 2013; 2013: 917068
    CrossrefPubMedSearch in Google Scholar
  • 9 Homaira N, Rawlinson W, Snelling TL, Jaffe A. Effectiveness of palivizumab in preventing RSV hospitalization in high risk children: a real-world perspective. Int J Pediatr 2014; 2014: 571609
    CrossrefPubMedSearch in Google Scholar
  • 10 Moore HC, de Klerk N, Richmond PC. et al. Effectiveness of palivizumab against respiratory syncytial virus: cohort and case series analysis. J Pediatr 2019; 214: 121-127.e1
    CrossrefPubMedSearch in Google Scholar
  • 11 Simon A, Gehrmann S, Wagenpfeil G, Wagenpfeil S. Palivizumab use in infants with Down syndrome-report from the German Synagis™ Registry 2009-2016. Eur J Pediatr 2018; 177 (06) 903-911
    CrossrefPubMedSearch in Google Scholar
  • 12 Kool-Houweling LM, Penning-van Beest FJ, Bezemer ID, van Lingen RA, Herings RM. Infants born before 32 weeks of gestation or with respiratory disease are most likely to receive palivizumab in the Netherlands. Acta Paediatr 2015; 104 (09) 927-932
    CrossrefPubMedSearch in Google Scholar
  • 13 Haerskjold A, Henriksen L, Way S. et al. The Danish National Prescription Registry in studies of a biological pharmaceutical: palivizumab—validation against two external data sources. Clin Epidemiol 2015; 7: 305-312
    CrossrefPubMedSearch in Google Scholar
  • 14 Wang DY, Saleem M, Paes BA, Mitchell I, Li A, Lanctôt KL. CARESS Investigators. Respiratory syncytial virus prophylaxis in neurologic and muscular disorders in the Canadian respiratory syncytial virus evaluation study of palivizumab. Pediatr Infect Dis J 2019; 38 (08) 775-780
    CrossrefPubMedSearch in Google Scholar
  • 15 Heljic S, Maksic H, Begic H. et al. Palivizumab prophylaxis of RSV infections in Bosnia and Herzegovina. J Pediatr Neonat Individual Med. 2016; 5: e050129
    PubMedSearch in Google Scholar
  • 16 Simon A, Gehrmann S, Wagenpfeil G, Wagenpfeil S. Use of palivizumab in Germany–report from the German Synagis™ Registry 2009–2016. Klin Padiatr 2018; 230 (05) 263-269
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Paes B, Mitchell I, Li A, Lanctôt KL. Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatr 2012; 171 (05) 833-841
    CrossrefPubMedSearch in Google Scholar
  • 18 Luna MS, Manzoni P, Paes B. et al. Expert consensus on palivizumab use for respiratory syncytial virus in developed countries. Paediatr Respir Rev 2020; 33: 35-44
    PubMedSearch in Google Scholar
  • 19 Manzoni P, Paes B, Lanctôt KL. et al. Outcomes of infants receiving palivizumab prophylaxis for respiratory syncytial virus in Canada and Italy. Pediatr Infect Dis J 2017; 36 (01) 2-8
    CrossrefPubMedSearch in Google Scholar
  • 20 Kashiwagi T, Okada Y, Nomoto K. Palivizumab prophylaxis against respiratory syncytial virus infection in children with immunocompromised conditions or down syndrome: a multicenter, post-marketing surveillance in Japan. Paediatr Drugs 2018; 20 (01) 97-104
    CrossrefPubMedSearch in Google Scholar
  • 21 Berger TM, Fontana M, Stocker M. The journey towards lung protective respiratory support in preterm neonates. Neonatology 2013; 104 (04) 265-274
    CrossrefPubMedSearch in Google Scholar
  • 22 Gonska T, Ratjen F. Newborn screening for cystic fibrosis. Expert Rev Respir Med 2015; 9 (05) 619-631
    CrossrefPubMedSearch in Google Scholar
  • 23 Berry JG, Hall M, Cohen E, O'Neill M, Feudtner C. Ways to identify children with medical complexity and the importance of why. J Pediatr 2015; 167 (02) 229-237
    CrossrefPubMedSearch in Google Scholar
  • 24 Law BJ, Langley JM, Allen U. 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 (09) 806-814
    CrossrefPubMedSearch in Google Scholar
  • 25 Paes BA, Craig C, Pigott W, Latchman A. Seasonal respiratory syncytial virus prophylaxis based on predetermined dates versus regional surveillance data. Pediatr Infect Dis J 2013; 32 (09) e360-e364
    CrossrefPubMedSearch in Google Scholar
  • 26 SPSS Inc. Released 2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc. USA; 2008
    Search in Google Scholar
  • 27 Baranov AA, Ivanov DO, Aliamovskaia GA. et al. Palivizumab: four seasons in Russia. Vestn Ross Akad Med Nauk 2014; ;(7-8): 54-66, 68
    CrossrefPubMedSearch in Google Scholar
  • 28 Borecka R, Lauterbach R. Compliance with the RSV immunoprophylaxis dosing schedule in the Polish registry for palivizumab (2008-2014). Dev Period Med 2018; 22 (04) 308-314
    PubMedSearch in Google Scholar
  • 29 Lacaze-Masmonteil T, Rozé JC, Fauroux B. French Pediatricians' Group of Sunagis Patients' Name-Based Programs. Incidence of respiratory syncytial virus-related hospitalizations in high-risk children: follow-up of a national cohort of infants treated with Palivizumab as RSV prophylaxis. Pediatr Pulmonol 2002; 34 (03) 181-188
    CrossrefPubMedSearch in Google Scholar
  • 30 Bennett MV, McLaurin K, Ambrose C, Lee HC. Population-based trends and underlying risk factors for infant respiratory syncytial virus and bronchiolitis hospitalizations. PLoS One 2018; 13 (10) e0205399
    Search in Google Scholar
  • 31 American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134 (02) e620-e638
    Search in Google Scholar
  • 32 Bollani L, Baraldi E, Chirico G. et al; Italian Society of Neonatology. Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus (RSV). Ital J Pediatr 2015; 41: 97
    CrossrefPubMedSearch in Google Scholar
  • 33 Al Aql F, Al-Hajjar S, Bin Mahmoud L. et al. Int J Pediatr. Adolesc Med 2016; 3: 38-42
    PubMedSearch in Google Scholar
  • 34 Frogel M, Nerwen C, Cohen A, VanVeldhuisen P, Harrington M, Boron M. Palivizumab Outcomes Registry Group. Prevention of hospitalization due to respiratory syncytial virus: results from the Palivizumab Outcomes Registry. J Perinatol 2008; 28 (07) 511-517
    CrossrefPubMedSearch in Google Scholar
  • 35 Hampp C, Saidi AS, Winterstein AG. Palivizumab utilization and compliance: trends in respiratory syncytial virus prophylaxis in Florida. J Pediatr 2010; 156 (06) 953-959.e1
    CrossrefPubMedSearch in Google Scholar
  • 36 Thorburn K. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child 2009; 94 (02) 99-103
    CrossrefPubMedSearch in Google Scholar
  • 37 Kang JM, Lee J, Kim YK. et al. Pediatric intensive care unit admission due to respiratory syncytial virus: retrospective multicenter study. Pediatr Int (Roma) 2019; 61 (07) 688-696
    CrossrefPubMedSearch in Google Scholar
  • 38 Paes B, Mitra S. Palivizumab for children with Down syndrome: is the time right for a universal recommendation?. Arch Dis Child 2019; 104 (08) 719-721
    CrossrefPubMedSearch in Google Scholar