提示: 手机请竖屏浏览!

单次注射nirsevimab预防早产儿呼吸道合胞病毒感染
Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants


M. Pamela Griffin ... 妇产科和儿科 • 2020.07.30
相关阅读
• 儿童病毒性毛细支气管炎 • 低收入和中等收入国家儿童的重症肺炎病因

摘要


背景

呼吸道合胞病毒(RSV)是婴儿下呼吸道感染的最常见原因,目前在预防健康婴儿RSV方面有需求。nirsevimab是一种处于研发阶段的长半衰期单克隆抗体,研发该药物的目的是通过单次肌内注射在整个RSV流行季对婴儿产生防护作用。

 

方法

在既有北半球国家也有南半球国家参与的这项试验中,我们在健康早产儿(出生时胎龄为29周0日至34周6日)中评估了nirsevimab对RSV相关下呼吸道感染的预防效果。我们以2∶1的比例将婴儿随机分组,两组分别在RSV流行季开始时接受nirsevimab(50 mg)或安慰剂单次肌内注射。主要终点是截至给药后150日,就医的RSV相关下呼吸道感染。次要效果终点为截至给药后150日,因RSV相关下呼吸道感染住院。

 

结果

从2016年11月至2017年11月,共计1,453名婴儿被随机分组,分别在RSV流行季开始时接受nirsevimab(969名婴儿)或安慰剂(484名婴儿)给药。在nirsevimab预防组中,就医的RSV相关下呼吸道感染发生率(2.6%[25名婴儿] vs. 9.5%[46名婴儿];P<0.001)比安慰剂组低70.1%(95%置信区间[CI],52.3~81.2),因RSV相关下呼吸道感染住院的发生率(0.8%[8名婴儿] vs. 4.1%[20名婴儿];P<0.001)比安慰剂组低78.4%(95% CI,51.9~90.3)。在给药后的整个150日期间,以及在不同地点和对于不同RSV亚型,均存在上述差异。两个试验组的不良事件相似,无显著的过敏反应。

 

结论

与安慰剂相比,健康早产儿单次注射nirsevimab在整个RSV流行季减少了就医的RSV相关下呼吸道感染和住院(由阿斯利康公司和赛诺菲巴斯德公司资助,在ClinicalTrials.gov注册号为NCT02878330)。





作者信息

M. Pamela Griffin, M.D., Yuan Yuan, Ph.D., Therese Takas, B.S., Joseph B. Domachowske, M.D., Shabir A. Madhi, M.B., B.Ch., Ph.D., Paolo Manzoni, M.D., Ph.D., Eric A.F. Simões, M.D., Mark T. Esser, Ph.D., Anis A. Khan, Ph.D., Filip Dubovsky, M.D., Tonya Villafana, Ph.D., and John P. DeVincenzo, M.D. for the Nirsevimab Study Group*
From AstraZeneca, Gaithersburg, MD (M.P.G., Y.Y., T.T., M.T.E., A.A.K., F.D., T.V.); SUNY Upstate Medical University, Syracuse, NY (J.B.D.); Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, and Department of Science and Technology/National Research Foundation South African Research Chair, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg (S.A.M.); the Division of Pediatrics and Neonatology, Department of Maternal, Neonatal, and Infant Medicine, Nuovo Ospedale Degli Infermi, Biella, and Neonatology and NICU, Sant’Anna Hospital, AOU Città della Salute e della Scienza, Turin — both in Italy (P.M.); the University of Colorado School of Medicine, Aurora (E.A.F.S.); and the Children’s Foundation Research Institute at Le Bonheur Children’s Hospital, Memphis, TN (J.P.D.V.). Address reprint requests to Dr. Villafana at R&D Biopharmaceuticals, AstraZeneca, 1 MedImmune Way, Gaithersburg, MD 20878, or at tonya.villafana@astrazeneca.com. *A list of investigators in the Nirsevimab Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Shi T, McAllister DA, O’Brien KL, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 2017;390:946-958.

2. Pneumonia Etiology Research for Child Health (PERCH) Study Group. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet 2019;394:757-779.

3. Jain S, Williams DJ, Arnold SR, et al. Community-acquired pneumonia requiring hospitalization among U.S. children. N Engl J Med 2015;372:835-845.

4. Miller EK, Gebretsadik T, Carroll KN, et al. Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years. Pediatr Infect Dis J 2013;32:950-955.

5. Carroll KN, Gebretsadik T, Griffin MR, et al. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan. Pediatrics 2008;122:58-64.

6. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med 2001;344:1917-1928.

7. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009;360:588-598.

8. Hall CB. The burgeoning burden of respiratory syncytial virus among children. Infect Disord Drug Targets 2012;12:92-97.

9. Hall CB, Walsh EE. Respiratory syncytial virus. In: Feigen RD, Demmler-Harrison GJ, Cherry JD, Kaplan SL, eds. Textbook of pediatric infectious disease. 6th ed. Philadelphia: W.B. Saunders, 2009:2462-2487.

10. Anderson EJ, DeVincenzo JP, Simões EAF, et al. SENTINEL1: two-season study of respiratory syncytial virus hospitalizations among U.S. infants born at 29 to 35 weeks’ gestational age not receiving immunoprophylaxis. Am J Perinatol 2020;37:421-429.

11. Giersing BK, Karron RA, Vekemans J, Kaslow DC, Moorthy VS. Meeting report: WHO consultation on respiratory syncytial virus (RSV) vaccine development, Geneva, 25-26 April 2016. Vaccine 2019;37:7355-7362.

12. Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969;89:422-434.

13. Mazur NI, Higgins D, Nunes MC, et al. The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect Dis 2018;18(10):e295-e311.

14. Groothuis JR, Simoes EA, Levin MJ, et al. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. N Engl J Med 1993;329:1524-1530.

15. 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;102:531-537.

16. 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.

17. Feltes TF, Sondheimer HM, Tulloh RM, et al. A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease. Pediatr Res 2011;70:186-191.

18. Carbonell-Estrany X, Simões EA, Dagan R, et al. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Pediatrics 2010;125(1):e35-e51.

19. O’Brien KL, Chandran A, Weatherholtz R, et al. Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy Native American infants: a phase 3 randomised double-blind placebo-controlled trial. Lancet Infect Dis 2015;15:1398-1408.

20. Synagis (palivizumab): highlights of prescribing information. Gaithersburg, MD: MedImmune, 2017.

21. 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(2):e620-e638.

22. Joint Committee on Vaccination and Immunisation statement on immunisation for respiratory syncytial virus. 2010 (https://webarchive.nationalarchives.gov.uk/20120907151316/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@ab/documents/digitalasset/dh_120395.pdf. opens in new tab).

23. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: final data for 2016. Natl Vital Stat Rep 2018;67(1):1-55.

24. Simões EA, DeVincenzo JP, Boeckh M, et al. Challenges and opportunities in developing respiratory syncytial virus therapeutics. J Infect Dis 2015;211:Suppl 1:S1-S20.

25. Zhu Q, McLellan JS, Kallewaard NL, et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci Transl Med 2017;9(388):eaaj1928-eaaj1928.

26. Robbie GJ, Criste R, Dall’acqua WF, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother 2013;57:6147-6153.

27. Griffin MP, Khan AA, Esser MT, et al. Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob Agents Chemother 2017;61(3):e01714-e01716.

28. Villafana T, Falloon J, Griffin MP, Zhu Q, Esser MT. Passive and active immunization against respiratory syncytial virus for the young and old. Expert Rev Vaccines 2017;16:1-13.

29. Domachowske JB, Khan AA, Esser MT, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J 2018;37:886-892.

30. Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004;159:702-706.

31. Karron RA, Zar HJ. Determining the outcomes of interventions to prevent respiratory syncytial virus disease in children: what to measure? Lancet Respir Med 2018;6:65-74.

32. Robbie GJ, Zhao L, Mondick J, Losonsky G, Roskos LK. Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children. Antimicrob Agents Chemother 2012;56:4927-4936.

33. Chu HY, Tielsch J, Katz J, et al. Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal. J Clin Virol 2017;95:90-95.

34. Nyiro JU, Sande CJ, Mutunga M, et al. Absence of association between cord specific antibody levels and severe respiratory syncytial virus (RSV) disease in early infants: a case control study from coastal Kenya. PLoS One 2016;11(11):e0166706-e0166706.

35. Munoz FM, Madhi S, Swamy GK, et al. Phase 3 PREPARE study: efficacy and safety of an RSV vaccine administered to pregnant women for the prevention of RSV lower respiratory tract infection in infants. Presented at the 27th Annual Meeting of the European Society for Paediatric Infectious Diseases, Ljubljana, Slovenia, May 6–11, 2019.

服务条款 | 隐私政策 | 联系我们