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Tricco AC, Zarin W, Cardoso R, et al. Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis. BMJ. 2018 Oct 25;363:k4029.
Area Score
Public Health
Family Medicine (FM)/General Practice (GP)
General Internal Medicine-Primary Care(US)
Infectious Disease

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.


Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

Summary: the new shingles vaccine is more effective but hurts more at the injection site. The article is fairly easy to read and/or skim.

General Internal Medicine-Primary Care(US) rater

This is helpful but ultimately we need point-of-care information with absolute risk for shingles with and without the vaccine and for how long there is protection. My reading of prior data is that this is a small benefit for patients with small risks and that the most vulnerable patients are at least protected.

Infectious Disease rater

This carefully done meta-analysis should be helpful in increasing uptake of the new shingles vaccine.

Public Health rater

As an infection preventionist and Public Health specialist, I find this review very useful, although the vaccine is not yet available in my country. It shows that the vaccine is useful for the prevention of herpes zoster infection, as measured by laboratory or doctor-confirmed cases and suspected cases with no statistically significant differences with the live attenuated vaccine for serious adverse events. It is really an important review since herpes zoster is a serious problem in immunocompromised patients, and they cannot receive live vaccines.