GSK, Wavre, Belgium.
GSK, Rockville, Maryland, USA.
J Am Geriatr Soc. 2021 Mar;69(3):744-752. doi: 10.1111/jgs.16917. Epub 2020 Nov 16.
BACKGROUND/OBJECTIVES: Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes.
DESIGN/SETTING: Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods.
PARTICIPANTS/INTERVENTION: In the two parent studies, participants aged ≥50 years (ZOE-50 study) and ≥70 years (ZOE-70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo.
In the current ZOE-Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety.
Of 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre-frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50-59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). The RZV group demonstrated robust anti-gE antibody and gE-specific CD4 responses, with mean concentrations remaining above pre-vaccination levels at least 3 years post-dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty.
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. RZV significantly reduced the risk of herpes zoster across all frailty subgroups.
背景/目的：衰弱参与者在随机试验中往往代表性不足，这引发了对真实环境中干预措施结果的质疑。衰弱与易患疾病和不良健康结果密切相关。我们研究了衰弱对重组带状疱疹疫苗（RZV）临床结果的影响。
设计/设置：汇总了两项先前进行的 RZV Ⅲ期随机试验的数据。这两项主要试验在同一研究地点同时进行，使用相同的方法。
参与者/干预措施：在两项主要研究中，年龄≥50 岁（ZOE-50 研究）和≥70 岁（ZOE-70 研究）的参与者分别按 1:1 随机分配接受两剂 RZV 或安慰剂。
在当前的 ZOE-Frailty 研究（NCT03563183）中，使用先前验证的方法创建了衰弱指数。根据衰弱状态评估的临床结果包括疫苗效力、免疫原性、反应原性和安全性。
在汇总的 ZOE-50 和 ZOE-70 总接种队列中，有 29305 名参与者，其中 92%纳入了本研究。平均年龄为 68.8 岁；58.1%为女性；45.6%为轻度衰弱，11.3%为衰弱。衰弱参与者的比例随年龄增加而增加，从 50-59 岁的 5.7%到≥80 岁的 22.7%。RZV 疫苗对带状疱疹的效力>90%，适用于所有衰弱亚组（非衰弱：95.8%（95%置信区间=91.6-98.2），轻度衰弱：90.4%（84.4-94.4），衰弱：90.2%（75.4-97.0））。RZV 组表现出强大的抗 gE 抗体和 gE 特异性 CD4 反应，在所有衰弱亚组中，至少在接受两剂疫苗后 3 年，平均浓度仍保持在接种前水平之上。在 RZV 组中，报告的不良事件的参与者比例随衰弱程度的增加而呈下降趋势。
在主要的 ZOE 研究中，相对非限制性的纳入/排除标准导致了一系列包括虚弱和轻度虚弱的老年参与者。RZV 显著降低了所有衰弱亚组的带状疱疹风险。
