Desmond Curran1, Joon H Kim2, Sean Matthews3, Christophe Dessart1, Myron J Levin4, Lidia Oostvogels1, Megan E Riley2, Kenneth E Schmader5, Anthony L Cunningham6, Shelly A McNeil7, Anne E Schuind2, Melissa K Andrew8. 1. GSK, Wavre, Belgium. 2. GSK, Rockville, Maryland, USA. 3. Freelance c/o GSK, Wavre, Belgium. 4. Departments of Pediatrics and Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 5. Division of Geriatrics, Duke University Medical Center and GRECC, Durham Veterans Affairs Medical Center, Durham, North Carolina, USA. 6. The Westmead Institute for Medical Research, Westmead, University of Sydney, Sydney, Australia. 7. Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, Canada. 8. Division of Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax, Canada.
Abstract
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. MEASUREMENTS: 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. RESULTS: 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 CD42+ 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. CONCLUSION: 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.
RCT Entities:
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. MEASUREMENTS: 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. RESULTS: 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 CD42+ 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. CONCLUSION: 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.
Authors: Charles T Semelka; Michael E DeWitt; Kathryn E Callahan; David M Herrington; Martha A Alexander-Miller; Joshua O Yukich; Iqra Munawar; Lewis H McCurdy; Michael A Gibbs; William S Weintraub; John W Sanders Journal: J Gerontol A Biol Sci Med Sci Date: 2022-07-05 Impact factor: 6.591
Authors: Charles T Semelka; Michael E DeWitt; Maria W Blevins; Beth C Holbrook; John W Sanders; Martha A Alexander-Miller Journal: Res Sq Date: 2022-08-01
Authors: Desmond Curran; Elizabeth M La; Ahmed Salem; David Singer; Nicolas Lecrenier; Sara Poston Journal: Hum Vaccin Immunother Date: 2022-01-20 Impact factor: 3.452