By Richard R. Watkins, MD, MS, FACP

Associate Professor of Internal Medicine, Northeast Ohio Medical University; Division of Infectious Diseases, Cleveland Clinic Akron General Medical Center, Akron, OH

Dr. Watkins reports that he has received research support from Actavis.

SYNOPSIS: An observational study from Kaiser Permanente Southern California showed that while the shingles vaccine reduces the risk of herpes zoster, there is a major decline in effectiveness over just eight years in older adults.

SOURCE: Tseng HF, Harpaz R, Luo Y, et al. Declining effectiveness of herpes zoster vaccine in adults aged ≥ 60 years. Clin Infect Dis 2016;213:1872-1875.

Administration of the herpes zoster (HZ) vaccine to adults ≥ 60 years of age has been part of routine clinical practice since 2006, based on recommendations from the Advisory Committee on Immunization Practices (ACIP). But subsequent research has questioned the long-term effectiveness of the vaccine. Therefore, Tseng and colleagues sought to clarify the amount of protection the HZ vaccine delivers for adults ≥ 60 years of age who were part of a large and diverse cohort.

Study participants were members of Kaiser Permanente Southern California and were identified through electronic medical records. There were two cohorts: 1) members who were vaccinated against HZ between 2007 and 2014 at the age of ≥ 60 years and 2) randomly sampled unvaccinated members ≥ 60 years with similar demographics who were matched at a ratio of 3:1 to the vaccine cohort. Exclusion criteria included having an episode of HZ one year prior and 30 days after the index date or being immunocompromised, which included HIV infection, hematologic malignancies, or taking immunosuppressive agents one year before the index date. Vaccine effectiveness by follow-up year was estimated using 1-adjusted hazard ratio (HR).

The vaccinated cohort had 176,078 members and the unvaccinated cohort had 528,234. There were 8.0 cases/1,000 person-years (95% CI, 7.8-8.2) of HZ in the vaccine group and 14.4 cases/1,000 person-years (95% CI, 14.2-14.6) in the unvaccinated ones. Receiving the vaccine was associated with a reduced risk of HZ (adjusted HR, 0.51; 95% CI, 0.49-0.52). The effectiveness of the vaccine declined each year of follow-up; at one year, it was 68.7% effective (95% CI, 66.3%-70.9%) but by year eight, it was down to 4.2% (95% CI, -24% to 25.9%). The cumulative risk for developing HZ in the vaccinated group over the eight-year period was 7.0% vs. 10.5% in the unvaccinated group (P < 0.05).

COMMENTARY

This large study showed that the beneficial effect of the HZ vaccine declines rapidly, and after eight years seems to offer little protection. Nevertheless, receiving the vaccine was still better in terms of HZ protection than being unvaccinated. Therefore, the current recommendation that adults > 60 years of age receive the HZ vaccine is still valid. But the study raised an important question: Should revaccination be considered, especially since increasing age heightens the risk for HZ? If so, what is the optimal interval? Every five years? Thus, more studies are needed to determine an optimal re-dosing strategy. As Tseng and colleagues mention, an investigational HZ vaccine seems to be more immunogenic in elderly individuals. Perhaps this new vaccine might alleviate the need for re-dosing, leading to reduced costs and, hopefully, better protection against HZ. Modification of the current HZ vaccine to make it more immunogenic is another potential approach.

The study has several strengths. The size and diversity of the cohorts was impressive, making the findings more generalizable to the broader population. Also, the investigators limited the analysis to subjects who were not lost to follow-up. A weakness of the study is the observational design, which could have introduced selection bias due to unmeasured variables. Another is that the electronic data could have been incomplete or biased from misclassification.

One important outcome that was not measured in the study was the effectiveness of the vaccine in preventing post-herpetic neuralgia (PHN). It would be interesting to determine if there is a decline in the effectiveness of the vaccine over time in preventing PHN. However, as noted by the authors, ascertainment bias is a potential pitfall for such an investigation.