Abstract & Commentary
Herpes Zoster Vaccination Indication Extended to Younger Individuals
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
ZOSTAVAX®, which had previously received FDA approval for prevention of herpes zoster (HZ) and post-herpetic neuralgia in individuals 60 years of age and older, had its approval extended to include people 50-59 years of age on March 24, 2011.1,2 This age group had been excluded from the Phase 3 trial that led to approval of the vaccine in the older group, presumably because of their lower incidence of HZ, which is only approximately 5 per 1,000 per year. The observation that the immunogenicity of the vaccine was significantly greater in younger than older individuals suggested that it might nonetheless be possible to demonstrate protective efficacy in the former group.
The investigators enrolled 22,439 individuals aged 50-59 years, randomizing them in a 1:1 ratio to receive either one dose of ZOSTAVAX or placebo, and followed them for a minimum of 1 year. Subsequent analysis identified 30 confirmed cases of HZ in the ZOSTAVAX group (from among 109 suspected cases) and 99 confirmed cases of HZ in the placebo group (of 168 suspected). In an intent-to-treat analysis, the estimated protective efficacy of the vaccine with regard to the development of zoster was 69.8% (95% confidence interval, 54.7%-79.8%) and was greater in females (73.8%) than males (55.0%). Vaccine efficacy was stable from entry to 1.5 years, but there were insufficient subjects with longer follow-up to estimate efficacy beyond that time. Protection is likely to persist for at least the 4-year window demonstrated in the previous study of older individuals.
The vaccine was well tolerated, although injection site pain, swelling, and/or erythema occurred in 63.6% of vaccine recipients and only 14.0% of those receiving placebo. These reactions were generally mild. The incidence of serious adverse reactions (SAE) was similar in the two groups. There was one vaccine-related SAE reported in a 52-year-old white female who experienced anaphylaxis shortly after receipt of ZOSTAVAX. She was emergently treated and had a full recovery. Of interest is that deaths occurred less frequently in the vaccine group than in the placebo group, 18 and 30, respectively.
While the incidence in this age group is lower relative to older individuals, shingles affects approximately 200,000 healthy people between the ages of 50 and 59 per year in the United States. FDA approval will pressure third party payers to reimburse for the cost of the vaccine, which is not inconsequential.
- Summary Basis for Regulatory Action. Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM249230.pdf.
- ZOSTAVAX® (Zoster Vaccine Live). Available at: www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM132831.pdf.