Dataset Information

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.

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://clinicaltrials.gov, NCT01165177 (ZOE-50), NCT01165229 (ZOE-70).

SUBMITTER: Dagnew AF

PROVIDER: S-EPMC7937016 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Background The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity. Methods The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA. Results VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2). Conclusion Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity. Funding: GlaxoSmithKline Biologicals SA. Disclosures All authors: No reported disclosures.

Project description:Abstract Background Patients with hematologic malignancies treated with anticancer immunosuppressive therapies (ITs) are at increased risk of herpes zoster (HZ). In a previous report of this phase 3, observer-blind, multicenter trial (NCT01767467), the adjuvanted recombinant zoster vaccine (RZV) was shown to be immunogenic and well-tolerated in ?18 years of age patients with hematologic malignancies who completed or were undergoing anticancer IT.1 Here we report end-of-study results from the same trial. Methods Participants were randomized 1:1 to receive 2 doses of RZV or placebo (PL) 1–2 months apart, either ?10 days before or after a cancer therapy cycle, or 10 days to 6 months after cancer therapy ended. Humoral and cell-mediated immune (CMI) responses were evaluated at 1 month and 12 months post-dose 2 (month 2 and month 13, respectively). Confirmatory objectives were to evaluate humoral response rate to RZV and to compare humoral immune responses to RZV and PL at month 2 excluding either subjects with chronic lymphocytic leukemia and non-Hodgkin B-cell lymphoma (NHBCL), or only those with NHBCL. Efficacy against HZ was explored in a post-hoc analysis of confirmed HZ cases. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were recorded throughout the study. Results Of the 562 (RZV: 283, PL: 279) treated participants, 415 (RZV: 217, PL: 198)/310 (RZV: 168, PL: 142) were included in the according-to-protocol (ATP) cohort for humoral immunogenicity/immune persistence. The ATP sub-cohort for CMI included 132 (RZV: 69, PL: 63) participants at month 2 and 100 (RZV: 54, PL: 46) at month 13. All confirmatory immunogenicity objectives were met (Table 1). RZV efficacy against HZ, assessed post-hoc, was 87.2% (Table 2). RZV was more reactogenic than PL. The occurrence of unsolicited AEs, SAEs, and pIMDs was similar between the study groups (Table 3). Conclusion RZV induced robust humoral and cellular immune responses and showed an effect in the reduction of HZ incidence in patients with hematologic malignancies who completed or were undergoing anticancer IT. No safety concerns were identified. Reference 1. Oostvogels et al. IDWeek2017, abs 1344. Funding. GlaxoSmithKline Biologicals SA. Disclosures A. F. Dagnew, GSK: Employee and Shareholder, Salary. J. Murphy, GSK: Investigator, Research support. S. A. McNeil, GSK group of companies: Grant Investigator, Research grant and Research support. B. Salaun, GSK group of companies: Employee and Shareholder, Salary. E. Di Paolo, GSK group of companies: Employee, Salary. L. Campora, GSK group of companies: Employee and Shareholder, Salary. M. López-Fauqued, GSK group of companies: Employee, Salary. M. El Idrissi, GSK group of companies: Employee, Salary. A. Schuind, GSK: Employee, Salary. T. C. Heineman, GSK group of companies: Consultant, Employee and Shareholder, Consulting fee and Salary. P. Van Den Steen, GSK: Employee and Shareholder, Restricted shares and Salary. L. Oostvogels, GSK: Employee, Salary and Stock and stock options.

Project description:IntroductionThis study aimed to update cost-effectiveness and public health impact estimates of the two-dose recombinant zoster vaccine (RZV) compared with no vaccination against herpes zoster (HZ) in the Japanese population aged 65 years. List price of the vaccine and latest RZV efficacy and waning estimates were incorporated.MethodsA multicohort static Markov model with a cycle length of 1 year was used to follow a hypothetical cohort of one million people aged 65 years over their remaining lifetime (base case). Age-stratified vaccine efficacy and waning rates were updated on the basis of the latest clinical trial data (interim ZOE-LTFU; NCT02723773). First-dose coverage was assumed at 40%, and second-dose compliance was assumed at 95%. Costs and outcomes were discounted at 2% annually, and the incremental cost-effectiveness ratio (ICER) was calculated from payer and societal perspectives. The societal perspective considered productivity loss due to suffering HZ, or due to suffering HZ and time required for vaccination. Sensitivity analyses explored the overall uncertainties in the model. Scenario analyses for Japanese adults aged 50, 60, 70, 80, ≥ 50, and ≥ 65 years (main scenario) were conducted. An ICER below ¥5-6 million/quality-adjusted life-year (QALY) was considered cost-effective.ResultsRZV was estimated to prevent 71,423 HZ cases and 15,858 post-herpetic neuralgia (PHN) cases per million people aged 65 years compared with no vaccine in Japan. The ICER was ¥4,205,515 from a payer perspective and was most sensitive to assumptions regarding vaccine efficacy waning, proportion of patients with HZ developing PHN, and HZ incidence. From societal perspectives, ICERs were ¥3,854,192 (productivity loss from suffering HZ only) and ¥4,622,212 (productivity loss from suffering HZ and time required for vaccination). Overall, the results were considered robust under extensive sensitivity and scenario analyses.ConclusionVaccination against HZ with RZV is cost-effective compared with no vaccination in Japanese adults aged 65 years.