PIN11 - The Comparative Efficacy, Safety, And Reactogenicity, of Herpes Zoster Vaccines: A Network Meta-Analysis

Abstract

To estimate the relative efficacy, safety, and reactogenicity of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials. A systematic literature review evaluated two different HZ vaccines: HZ adjuvanted subunit (HZ/su) and Zoster Vaccine Live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (against HZ and postherpetic neuralgia (PHN)), safety (serious adverse events), 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. HZ/su demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VEHZ/su=0.92 (95% confidence interval (95%CI): 0.88, 0.94), VEZVL=0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VEHZ/su=0.91 (95%CI: 0.87, 0.94), VEZVL=0.37 (95%CI: 0.25, 0.48)). Similarly, HZ/su demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VEHZ/su=0.89 (95%CI: 0.70, 0.96), VEZVL=0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VEHZ/su=0.89 (95%CI: 0.69, 0.96), VEZVL=0.67 (95%CI: 0.44, 0.80). The 95%CIs of the differences of VEHZ/su and VEZVL estimates did not contain 0, indicating that these were statistically significant. HZ/su 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. There were no statistically significant differences found between HZ/su and any formulation of ZVL or placebo for serious adverse events. HZ/su is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA when compared to ZVL. As anticipated with an adjuvanted vaccine, HZ/su results in more reactogenicity following immunization, but no safety differences were found between HZ/su and ZVL.