Effectiveness of Recombinant Herpes Zoster Vaccine in the U.S. Medicare Population, 2018 to 2019, by Immunocompetence and Prior Receipt of Live Zoster Vaccine.

BACKGROUND: Recombinant zoster vaccine (RZV) was preferentially recommended over live zoster vaccine (ZVL) starting in 2018. OBJECTIVE: To assess RZV effectiveness using target trial emulation, accounting for prior receipt of ZVL and immunocompetence. DESIGN: Analysis 1 emulated 12 sequential trials of at least 12 months' duration in which treatment assignment was assessed by real-world vaccination in the month before each trial. Individuals could participate in multiple trials for which they were eligible (for example, no prior RZV vaccination). Pooled vaccine effectiveness (VE) was estimated across the trials using weighted Fine and Gray models with robust variance estimation. Risks were estimated from the cumulative incidence function. Analysis 2 used the same methods to estimate the VE of 2 RZV doses versus 1 dose, with 10 trials beginning 60 days from the first dose. SETTING: 20% random sample of fee-for-service Medicare beneficiaries covered by Parts A, B, and D between 2007 and 2019. PARTICIPANTS: Medicare beneficiaries aged 65 years or older with continuous Part D coverage, 6 months of continuous coverage before trial enrollment, no claims for herpes zoster (HZ) since 2007, and no prior RZV vaccination. INTERVENTION: 1 or 2 RZV doses. MEASUREMENTS: Outcomes were HZ, HZ ophthalmicus, and postherpetic neuralgia. Covariates were age, sex, race, ethnicity, prior ZVL receipt, and immunocompetence. RESULTS: Vaccine effectiveness against any HZ outcome was 56.1% (95% CI, 53.1% to 59.0%), with similar VE between immunocompetent (56.5% [CI, 53.2% to 59.5%]) and immunocompromised (54.2% [CI, 44.7% to 62.1%]) individuals. Individuals vaccinated with ZVL in the past 10 years benefited from RZV. A second RZV dose conferred an additional 67.9% effectiveness against any HZ outcome. LIMITATION: Limited follow-up; covariate misclassification. CONCLUSION: Recombinant zoster vaccine is effective in older adults, including immunocompromised adults, and 2 doses were more effective than 1. Prior ZVL recipients should be revaccinated with RZV. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences.