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Klin Padiatr 2018; 230(05): 263-269
DOI: 10.1055/a-0595-7771
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Use of Palivizumab in Germany – Report from the German Synagis™ Registry 2009 – 2016

Einsatz von Palivizumab in Deutschland– Ergebnisse des Deutschen Synagis™ Patientenregisters 2009–2016
Arne Simon
1   Children's Hospital Medical Center, Paediatric Hematology and Oncology, Homburg, Germany
,
Susanne Gehrmann
2   Medical Unit Leader in the Medical Affairs Department, AbbVie Deutschland GmbH & Co.KG, Wiesbaden, Wiesbaden, Germany
,
Gudrun Wagenpfeil
3   Institutes for Medical Biometry, Epidemiology and Medical Informatics (IMBEI), Saarland University, Campus Homburg, Homburg, Germany
,
Stefan Wagenpfeil
3   Institutes for Medical Biometry, Epidemiology and Medical Informatics (IMBEI), Saarland University, Campus Homburg, Homburg, Germany
› Author Affiliations
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Publication History

Publication Date:
16 April 2018 (online)

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Abstract

Background Following national recommendations, palivizumab is administered in Germany to high-risk infants to prevent hospitalizations related to Respiratory Syncytial Virus infection.

Methods In this post marketing observational study (German SYNAGIS™ Registry) data on risk factors and the clinical course of children, who received at least one palivizumab injection between 2009–2016 (01 September to June 30) were entered into an internet-based data entry system by the attending physicians after informed consent.

Results 63 572 immunizations were documented for 12 729 evaluable patients (EVP) from 2009 to 2016, with an average of 5.0 immunizations per patient per season. 45% of infants received more than 5 injections. The predominant primary reason for immunization was premature birth (74%). In the EVP the rate of hospitalizations with causal relationship to RSV was 0.7% (=92/12 729) or 1.2% in a worst case scenario including patients with missing RSV test. In patients with hemodynamically significant congenital heart disease as main indication, RSV-related hospitalization rate was 0.8%. Intensive care was necessary in 16.9% (median duration 3 days), mechanical ventilation in 8.0%. No death related to RSV infection was reported.

Conclusion Keeping in mind the limitations of an uncontrolled prospective observational study, our results confirm the effectiveness and safety of palivizumab prophylaxis. The total number of patients with hsCHD is lower than expected. A better adjustment to the regional epidemiology would probably reduce the need for more than 5 injections.

Zusammenfassung

Hintergrund Palivizumab wird in Deutschland Hochrisikokindern nach den Empfehlungen der Fachgesellschaften verabreicht um Hospitalisierungen zu verhindern, die durch eine RSV Infektion bedingt sind.

Methoden In einer prospektiven Post-Marketing Surveillance Studie (Deutsches SYNAGIS™ Register) wurden Daten zu Risikofaktoren und zum Verlauf von Kindern erhoben, die zwischen 2009 und 2016 (1. Sept. – 30. Juni) mindestens eine Gabe Palivizumab erhalten haben. Nach Zustimmung der Sorgeberechtigten wurden die Daten von den behandelnden Ärzten in ein internetbasiertes Register eingegeben.

Ergebnisse Insgesamt erhielten zwischen 2009 und 2016 12 729 auswertbare Patienten (EVP) 63 572 Palivizumab Injektionen (im Mittel 5.0/Patient und Saison); 45% erhielten mehr als 5 Gaben. Frühgeburtlichkeit war die Hauptindikation (74%). Die Rate der RSV-bedingten Hospitalisierungen in der EVP betrug 0,7% (=92/12 729) bzw.1,2% in einem Worst-Case Szenario unter Einschluss der Patienten ohne RSV Test. Bei Patienten mit hämodynamisch signifikanter angeborener Herzerkrankung (hsCHD) betrug die RSV-bedingte Rehospitalisierungsrate 0,8%. Eine Intensivtherapie war in 16,9% erforderlich (mediane Dauer 3 Tage), invasive Beatmung in 8%. Es wurden keine RSV-bedingten Todesfälle berichtet.

Schlussfolgerung Vorbehaltlich der Limitationen eines nicht kontrollierten prospektiven Registers bestätigen die aktuellen Daten des Deutschen Synagis™ die Effektivität der Palivizumab Prophylaxe. Die absolute Anzahl der Kinder mit Hauptindikation hsCHD ist kleiner, als erwartet. Eine bessere Anpassung an die lokale Epidemiologie würde wahrscheinlich die Notwendigkeit von mehr als 5 Gaben pro Saison reduzieren.

Key words

palivizumab - Respiratory Syncytial Virus - preterm infants - congenital heart disease - bronchopulmonary dysplasia

Schlüsselwörter

Palivizumab - Respiratory Syncytial Virus - Frühgeborene - angeborene Herzerkrankung - Bronchopulmonale Dysplasie
 

  • References

  • 1 Al-Alaiyan S, Pollack P, Notario GF. Safety and pharmacokinetics of extended use of palivizumab in Saudi Arabian infants and children. Drugs in context 2015; Feb 27;4. pii: 212270. doi: 10.7573/dic.212270.
    PubMed
  • 2 American Academy of Pediatrics . Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134: e620-638
    CrossrefPubMedGoogle Scholar
  • 3 Blanken MO, Rovers MM, Molenaar JM. et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013; 368: 1791-1799
    CrossrefPubMedGoogle Scholar
  • 4 Chen JJ, Chan P, Paes B. et al. Serious Adverse Events in the Canadian Registry of Children Receiving Palivizumab (CARESS) for Respiratory Syncytial Virus Prevention. PLoS One 2015; 10: e0134711
    CrossrefPubMedGoogle Scholar
  • 5 Chi H, Hsu CH, Chang JH. et al. A novel six consecutive monthly doses of palivizumab prophylaxis protocol for the prevention of respiratory syncytial virus infection in high-risk preterm infants in Taiwan. PLoS One 2014; 9: e100981
    CrossrefPubMedGoogle Scholar
  • 6 Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI). Deutsche Gesellschaft für Pädiatrische Kardiologie (DGPK). Deutsche Gesellschaft für Pädiatrische Pneumonologie (DPP) et al. Stellungnahme zur Prophylaxe von schweren RSV-Erkrankungen bei Risikokindern mit Palivizumab. http://wwwdgpide/pdf/Palivizumab_LL_final_30Sep 2008pdf 2008
    PubMed
  • 7 Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI). Deutsche Gesellschaft für Pädiatrische Kardiologie (DGPK). Gesellschaft für Pädiatrische Pneumologie (GPP) et al. AWMF-LL 048-012 – Leitlinie zur Prophylaxe von schweren Erkrankungen durch Respiratory Syncytial Virus (RSV) bei Risikokindern 28. Oktober 2012. 2012
    PubMed
  • 8 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: 532-540
    CrossrefPubMedGoogle Scholar
  • 9 Geskey JM, Thomas NJ, Brummel GL. Palivizumab in congenital heart disease: should international guidelines be revised?. Expert Opin Biol Ther 2007; 7: 1615-1620
    CrossrefPubMedGoogle Scholar
  • 10 Glezen WP, Taber LH, Frank AL. et al. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 1986; 140: 543-546
    PubMedGoogle Scholar
  • 11 Gutfraind A, Galvani AP, Meyers LA. Efficacy and optimization of palivizumab injection regimens against respiratory syncytial virus infection. JAMA Pediatr 2015; 169: 341-348
    CrossrefPubMedGoogle Scholar
  • 12 La Via WV, Notario GF, Yu XQ. et al. Three monthly doses of palivizumab are not adequate for 5-month protection: A population pharmacokinetic analysis. Pulmonary pharmacology & therapeutics 2013 DOI: DOI: 10.1016/j.pupt.2013.03.007.
    PubMedGoogle Scholar
  • 13 Makari D, Checchia PA, Devincenzo J. Rationale for full-season dosing for passive antibody prophylaxis of respiratory syncytial virus. Hum Vaccin Immunother 2014; 10: 607-614
    CrossrefPubMedGoogle Scholar
  • 14 Paes B, Mitchell I, Li A. et al. Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005–2012) compared to other international registries. Clin Dev Immunol 2013; 2013: 917068
    PubMedGoogle Scholar
  • 15 Paes B, Mitchell I, Li A. et al. A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS). Eur J Clin Microbiol Infect Dis 2012; 31: 2703-2711
    CrossrefPubMedGoogle Scholar
  • 16 Parnes C, Guillermin J, Habersang R. et al. Palivizumab prophylaxis of respiratory syncytial virus disease in 2000–2001: results from The Palivizumab Outcomes Registry. Pediatr Pulmonol 2003; 35: 484-489
    CrossrefPubMedGoogle Scholar
  • 17 Resch B, Kurath-Koller S, Hahn J. et al. Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease. Eur J Clin Microbiol Infect Dis 2016; 35: 1165-1169
    CrossrefPubMedGoogle Scholar
  • 18 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: 707-712
    CrossrefPubMedGoogle Scholar
  • 19 Simon A, Nowak H, Sterz R. Use of Palivizumab in Germany: Data from 2002–2007. Klin Padiatr 2011; 223: 292-298
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Stockman LJ, Curns AT, Anderson LJ. et al. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997–2006. Pediatr Infect Dis J 2012; 31: 5-9
    CrossrefPubMedGoogle Scholar
  • 21 The IMpact-RSV Study Group . 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: 531-537
    CrossrefPubMedGoogle Scholar
  • 22 Weinberger DM, Warren JL, Steiner CA. et al. Reduced-Dose Schedule of Prophylaxis Based on Local Data Provides Near-Optimal Protection Against Respiratory Syncytial Virus. Clin Infect Dis 2015; 61: 506-514
    CrossrefPubMedGoogle Scholar
  • 23 Whelan B, Musters E, Murray A. et al. Review of the home care programmes for respiratory syncytial virus (RSV) prophylaxis in Ireland and The Netherlands. Drugs & therapy perspectives: for rational drug selection and use 2016; 32: 119-130
    PubMedGoogle Scholar
  • 24 Zembles TN, Gaertner KM, Gutzeit MF. et al. Implementation of American Academy of Pediatrics guidelines for palivizumab prophylaxis in a pediatric hospital. Am J Health Syst Pharm 2016; 73: 405-408
    CrossrefPubMedGoogle Scholar