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Meta-Analysis
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Efficacy, Effectiveness, and Safety of Herpes Zoster Vaccines in Adults Aged 50 and Older: Systematic Review and Network Meta-Analysis

Affiliations
Meta-Analysis

Efficacy, Effectiveness, and Safety of Herpes Zoster Vaccines in Adults Aged 50 and Older: Systematic Review and Network Meta-Analysis

Andrea C Tricco et al. BMJ.

Abstract

Objective: To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.

Design: Systematic review with bayesian meta-analysis and network meta-analysis.

Data sources: Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.

Eligibility criteria for study selection: Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.

Results: 27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).

Conclusions: Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.

Protocol registration: Prospero CRD42017056389.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare that all authors had financial support from the Canadian Institutes of Health Research Drug Safety and Effectiveness Network (DNM–137713); authors have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities to declare that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Study flow diagram
Fig 2
Fig 2
Distribution of Cochrane Collaboration Risk of Bias assessment (n=22 randomised controlled trials). The “other bias” item was scored as high risk of bias when studies were funded by private industries and included authors who are employed by vaccine manufacturers
Fig 3
Fig 3
Forest plot of estimated results from meta-analysis and network meta-analysis of vaccine efficacy outcomes in reducing cases of herpes zoster, herpes zoster ophthalmicus, and post-herpetic neuralgia. HZ/su=herpes zoster adjuvant recombinant subunit vaccine; ZVL=herpes zoster live attenuated vaccine
Fig 4
Fig 4
Forest plot of estimated results from meta-analysis and network meta-analysis of safety outcomes including, injection site, systemic, and serious adverse events, and withdrawal due to adverse events, as well as potential immune mediated diseases and death. HZ/su=herpes zoster adjuvant recombinant subunit vaccine; ZVL=herpes zoster live attenuated vaccine
Fig 5
Fig 5
Rank heat plot, summarising treatment hierarchy across all outcomes. Each circle represents an outcome and has been sectioned into the three interventions, adjuvant, recombinant subunit herpes zoster vaccine, live attenuated herpes zoster vaccine, and placebo. The performance of a particular treatment for each of the outcomes is interpreted based on three colours (worst to best): red (0%), yellow (50%), and green (100%)

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