Randomized trials often exclude participants who are frail or who have multiple comorbidities. That leaves unanswered questions about vaccine efficacy in a real?world setting, according to a new study.

The report in the Journal of the American Geriatric Society points out that frailty often is associated with low immune responses and poor clinical analysis with other vaccines. As a result, the industry-led study including researchers from the University of Colorado Anschutz Medical Campus in Aurora, sought to perform additional analysis of data from the ZOE studies, focusing on efficacy of the recombinant zoster vaccine (RZV), as well as immunogenicity, reactogenicity, and safety.

Researchers used pooled data from two previously conducted phase III randomized trials of RZV; the two trials were conducted concurrently at the same study sites using the same methods. Those trials involved participants aged 50 years and older (ZOE-50 study) and aged 70 years and older (ZOE-70 study), who were randomized 1:1 to receive two doses of RZV or placebo.

Most, 92%, of the 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort were included in the new study. Their mean age was 68.8 years, and 58.1% were women; 45.6% were prefrail and 11.3% were frail. The authors point out that the percentage of frail participants increased with age from 5.7% aged 50 to 59 years to 22.7% aged 80 years or older.

For the current ZOE-Frailty study, the researchers created a frailty index using previously validated methods. Vaccine efficacy, immunogenicity, reactogenicity, and safety were then assessed based on frailty status.

Results indicate that RZV vaccine efficacy against herpes zoster was greater than 90% for all frailty subgroups (nonfrail: 95.8% [95% CI = 91.6-98.2], prefrail: 90.4% [CI = 84.4-94.4], frail: 90.2% [CI = 75.4-97.0]). In fact, the researchers advise, the RZV group demonstrated robust anti-gE antibody and gE-specific CD42+ responses, with mean concentrations remaining above prevaccination levels at least 3 years postdose, in all frailty subgroups. Furthermore, in the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty, they write.

“The relatively nonrestrictive inclusion/exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre-frail older adults,” the authors conclude. “RZV significantly reduced the risk of herpes zoster across all frailty subgroups.”

The researchers explain how, with herpes zoster, VZV cell–mediated immune response declines with age, which correlates with an increase in incidence and severity of HZ, adding “Older adults are at an increased risk of having severe pain during the acute phase, and of developing complications such as postherpetic neuralgia (PHN), which can have a devastating impact on quality of life (QoL). Particularly in frail individuals, HZ can lead to an inability to recover the lifestyle, interests, and level of functional activity that existed before HZ, and may also be associated with depression.”

The researchers add that vaccines against other infections, such as influenza and pneumococcal disease, are generally less effective in older or frail individuals, pointing out, “Consequently, there is a paradox, that is, the people in most need of protection may benefit less from those vaccines.”
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