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The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis
Affiliation:1. GSK Canada, 7333 Mississauga Rd N, Mississauga, ON L5N 6L4, Canada;2. GSK, 20 Avenue Fleming, Wavre 1300, Belgium;3. GSK, Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex UB11 1BT, United Kingdom;4. Health Sciences North Research Institute, 41 Ramsey Lake Road, Sudbury P3E 5J1, Canada;5. Evidera, 7575 Trans-Canada Hwy, Suite 404, St-Laurent, Quebec H4T 1V6, Canada;6. ICON plc, Konrad-Zuse-Platz 11, 81829 München, Germany;7. ICON plc, De Molen 84, Houten 3995 AX, the Netherlands;8. ICON plc, Klarabergsviadukten 90 Hus D, Stockholm 111 64, Sweden
Abstract:BackgroundWe estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials.MethodsA systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age.ResultsRZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VERZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VEZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VERZV = 0.91 (95%CI: 0.87, 0.94), VEZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VERZV = 0.89 (95%CI: 0.70, 0.96), VEZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VERZV = 0.89 (95%CI: 0.69, 0.96), VEZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs.ConclusionRZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.
Keywords:Comparative efficacy  Herpes zoster  Post-herpetic neuralgia  Reactogenicity  Safety  Vaccine  ACIP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0040"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Advisory Committee on Immunization Practices  BIKEN"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0050"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  live attenuated Oka varicella vaccine manufactured by the Research Foundation for Microbial Diseases of Osaka University  CI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0060"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  confidence interval  CIQ"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0070"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Comité sur l’immunisation du Québec  FDA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0080"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Food and Drug Administration  HZ"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0090"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  herpes zoster  ID"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0100"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  intradermal  IM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0110"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  intramuscular  IRR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0120"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  incidence rate ratio  NACI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0130"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  National Advisory Committee on Immunization  NMA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0140"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  network meta-analysis  PHN"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0150"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  post-herpetic neuralgia  RCT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0160"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  randomised controlled trial  RZV"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0170"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  recombinant zoster vaccine  SAE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0180"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  serious adverse event  SC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0190"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  subcutaneous  SLR"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0200"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  systematic literature review  SPS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0210"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Shingles Prevention Study  VE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0220"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  vaccine efficacy  VZV"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0230"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  varicella zoster virus  ZEST"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0240"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Zoster Efficacy and Safety Trial  ZVL"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  k0250"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Zoster Vaccine Live
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