Advanced

Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine : 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial

Povey, Michael; Henry, Ouzama; Riise Bergsaker, Marianne A.; Chlibek, Roman; Esposito, Susanna; Flodmark, Carl Erik LU ; Gothefors, Leif; Man, Sorin; Silfverdal, Sven Arne and Štefkovičová, Mária, et al. (2019) In The Lancet Infectious Diseases 19(3). p.287-297
Abstract

Background: The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella. Methods: This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12–22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive... (More)

Background: The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella. Methods: This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12–22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499. Findings: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0–96·4) for MMRV and 67·2% (62·3–71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9–99·6) for MMRV and 89·5% (86·1–92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths. Interpretation: The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination. Funding: GlaxoSmithKline Biologicals.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet Infectious Diseases
volume
19
issue
3
pages
11 pages
publisher
Elsevier
external identifiers
  • scopus:85062007240
ISSN
1473-3099
DOI
10.1016/S1473-3099(18)30716-3
language
English
LU publication?
no
id
fa92d0b3-1b98-4c98-9445-01078c1f16d6
date added to LUP
2019-03-06 10:31:54
date last changed
2019-09-17 04:49:42
@article{fa92d0b3-1b98-4c98-9445-01078c1f16d6,
  abstract     = {<p>Background: The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella. Methods: This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12–22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499. Findings: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0–96·4) for MMRV and 67·2% (62·3–71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9–99·6) for MMRV and 89·5% (86·1–92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths. Interpretation: The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination. Funding: GlaxoSmithKline Biologicals.</p>},
  author       = {Povey, Michael and Henry, Ouzama and Riise Bergsaker, Marianne A. and Chlibek, Roman and Esposito, Susanna and Flodmark, Carl Erik and Gothefors, Leif and Man, Sorin and Silfverdal, Sven Arne and Štefkovičová, Mária and Usonis, Vytautas and Wysocki, Jacek and Gillard, Paul and Prymula, Roman},
  issn         = {1473-3099},
  language     = {eng},
  number       = {3},
  pages        = {287--297},
  publisher    = {Elsevier},
  series       = {The Lancet Infectious Diseases},
  title        = {Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine : 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial},
  url          = {http://dx.doi.org/10.1016/S1473-3099(18)30716-3},
  volume       = {19},
  year         = {2019},
}