Efficacy and serious adverse events profile of the adjuvanted recombinant zoster vaccine in adults with pre-existing potential immune-mediated diseases: a pooled post hoc analysis on two parallel randomized trials

Alemnew F Dagnew, Debora Rausch, Caroline Hervé, Toufik Zahaf, Myron J Levin, Anne Schuind, ZOE-50/70 study group, Alemnew F Dagnew, Debora Rausch, Caroline Hervé, Toufik Zahaf, Myron J Levin, Anne Schuind, ZOE-50/70 study group

Abstract

Abstract objective: In the ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials, the adjuvanted recombinant zoster vaccine (RZV) demonstrated ≥90% efficacy in preventing herpes zoster (HZ) in all age groups ≥50 years. Given the increased HZ risk associated with certain underlying autoimmune diseases or their treatment regimes, we conducted a post hoc analysis of RZV's efficacy against HZ and safety profile [specifically, the occurrence of serious adverse events (SAEs)] in ZOE-50/70 participants who reported pre-existing potential immune-mediated diseases (pIMDs) at enrolment and were not on immunosuppressive therapies.

Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomized to receive two doses of RZV or placebo 2 months apart. In this subgroup analysis of participants with at least one pIMD at enrolment, the efficacy was calculated for two-dose recipients who did not develop confirmed HZ before 30 days post-dose 2. SAE occurrence was evaluated for all participants who received at least one dose.

Results: Of the 14 645 RZV and 14 660 placebo recipients from the ZOE-50/70 studies, 983 and 960, respectively, reported at least one pre-existing pIMD at enrolment and were included in these analyses. The most frequent pre-existing conditions were psoriasis, spondyloarthropathy and RA. Efficacy against HZ was 90.5% (95% CI: 73.5, 97.5%) overall with the lowest being 84.4% (95% CI: 30.8, 98.3%) in the 70-79-year-old age group. SAEs and fatal SAEs were similar between RZV and placebo recipients.

Conclusion: In ZOE-50/70 participants with pre-existing pIMDs, RZV was highly efficacious against HZ and SAE incidence was similar between RZV and placebo recipients.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT01165177" title="See in ClinicalTrials.gov">NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).

Keywords: potential immune-mediated diseases; psoriasis; rheumatoid arthritis; spondyloarthropathy; vaccines; varicella-zoster virus.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Graphical abstract
Graphical abstract
Fig . 1
Fig. 1
Ten most common pIMDs in both groups at enrolment (TVC) Participants with pre-existing pIMDs were identified by querying the global medical history of the participants included in TVC with a customized Medical Dictionary for Regulatory Activities query for pIMDs [19]. Error bars represent 95% CI. pIMD: potential immune-mediated disease; Placebo: participants receiving placebo; RZV: participants receiving the adjuvanted recombinant zoster vaccine; TVC: total vaccinated cohort.
Fig . 2
Fig. 2
SAEs in participants with pre-existing pIMDs reported through 365 days post-last vaccine dose (TVC) SAEs by MedDRA SOC (framed) and PT are presented here. Per PT, only SAEs reported by ≥0.3% of RZV recipients are presented here. Error bars represent 95% CI. MedDRA: Medical Dictionary for Regulatory Activities; pIMD: potential immune-mediated disease; Placebo: participants receiving placebo; PT: preferred term; RZV: participants receiving the adjuvanted recombinant zoster vaccine; SAE: serious adverse event; SOC: system organ class; TVC: total vaccinated cohort; YOA: years of age.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7937016/bin/keaa424f3.jpg
Fig. 3 SAEs with fatal outcome in participants with pre-existing pIMDs reported during the entire study period (TVC) SAEs by MedDRA SOC (framed) and PT are presented here. Per PT, only SAEs reported by ≥0.3% of RZV recipients are presented here. Error bars represent 95% CI. MedDRA: Medical Dictionary for Regulatory Activities; pIMD: potential immune-mediated disease; Placebo: participants receiving placebo; PT: preferred term; RZV: participants receiving the adjuvanted recombinant zoster vaccine; SAE: serious adverse event; SOC: system organ class; TVC: total vaccinated cohort.

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