Currently a live attenuated herpes zoster vaccine (Zostavax®) is used for the national shingles immunisation schedule in the UK. An adjuvant recombinant subunit vaccine (Shingrix®) is now also approved in the EU. The purpose of this analysis was to compare the efficacy, effectiveness, and safety of the two vaccines in adults aged 50 and older. In the absence of any head-to-head trials, the authors used network meta-analysis techniques to compare the two vaccines indirectly.
A total of 5 RCTs (n=90,605) were included in the meta-analysis of laboratory or doctor confirmed cases of herpes zoster. The adjuvant recombinant subunit vaccine was statistically superior to placebo (vaccine efficacy 94%, 95% credible interval 79% to 98%) and the live attenuated vaccine (85%, 31% to 98%), whereas the live attenuated vaccine was not statistically different from placebo. Owing to a lack of data, the superiority of the adjuvant recombinant subunit vaccine over the live attenuated vaccine in reducing the number of cases of herpes zoster ophthalmicus and post-herpetic neuralgia was inconclusive.
In terms of adverse events, the adjuvant recombinant subunit vaccine was associated with a higher risk of adverse events at the injection site (1.79, 1.05 to 2.34) than those given the live attenuated vaccine. From the limited indirect evidence available there was no suggestion of any statistically significant differences for serious adverse events, withdrawals due to adverse events, potential immune mediated diseases, or death. However there is an ongoing RCT evaluating the relative safety of these two vaccines and this systematic review will need to be updated when the results of this are available.
The authors of a related editorial notes that the results of network meta-analyses need to be interpreted with caution if the combined studies are very heterogeneous and that the studies in this analysis varied substantially in sample size and duration. In addition the main analysis used the combination of both immunocompromised and immunocompetent patients – this led to the live attenuated vaccine becoming similar to placebo in preventing doctor or laboratory confirmed shingles (an earlier Cochrane review excluded trials involving participants with immunosuppressive disorders).
The latest guidance for healthcare professionals on vaccination against shingles, issued in March 2018, noted that the Joint Committee on Vaccination and Immunisation has Shingrix® under consideration for potential future use in the national programme.