Efficacy of the adjuvanted recombinant zoster vaccine (RZV) by sex,geographic region,and geographic ancestry/ethnicity: A post-hoc analysis of the ZOE-50 and ZOE-70 randomized trials

BackgroundHerpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity.MethodsIn 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229).ResultsVaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds.ConclusionsWhile the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.     

Patient report of herpes zoster pain: Incremental benefits of zoster vaccine live

IntroductionPain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California.MethodsZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0–10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients.ResultsWe interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR = 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR = 0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70 years versus those ≥70 years and was similar or lower in females versus males.ConclusionWe used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN.     

Safety of the adjuvanted recombinant zoster vaccine in adults aged 50 years or older. A phase IIIB,non-randomized,multinational, open-label study in previous ZOE-50 and ZOE-70 placebo recipients

BackgroundEfficacy of the adjuvanted recombinant zoster vaccine (RZV) against herpes zoster (HZ) was demonstrated in pivotal trials ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229). This study was designed to offer RZV to placebo recipients of these parent studies.MethodsVaccine safety and suspected HZ episode occurrence were assessed for 12 months following vaccination.ResultsOf the 14,550 eligible participants, 8687 received RZV and 97.8% completed the 2-dose schedule. During the 30-day post-vaccination period, 5175 (59.6%) participants experienced ≥ 1 unsolicited adverse event (AE), 4422 (50.9%) were vaccination-related. The most common AEs were injection-site reactions, pyrexia, and headache. During the study, 734 (8.4%) participants reported ≥ 1 serious AE (SAE) and 62 (0.7%) reported ≥ 1 potential immune-mediated disease (pIMD); 2 of each were assessed as vaccination-related. Suspected HZ episodes were reported by 30 participants (0.3%).ConclusionsNature and incidence of AEs, SAEs, and pIMDs were as expected and in line with the parent studies.     

Immunogenicity,reactogenicity and safety of 2 doses of an adjuvanted herpes zoster subunit vaccine administered 2, 6 or 12 months apart in older adults: Results of a phase III,randomized, open-label,multicenter study

BackgroundIn phase III trials, 2 doses of a herpes zoster (HZ) subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01_B Adjuvant System) administered 2-months apart in older adults (≥50 and ≥70 years) demonstrated >90% efficacy in preventing HZ and had a clinically acceptable safety profile. Here we report immunogenicity, reactogenicity and safety following administration of 2 HZ/su doses at intervals longer than 2 months.MethodsIn this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2.Results346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination.ConclusionsImmune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals.Clinical Trials Registration: Clinicaltrials.gov (NCT01751165).     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

The burden of herpes zoster disease in Norway

BackgroundNo national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program.MethodsWe linked data from several health registries to identify medically attended HZ cases during 2008–2014 and HZ-associated deaths during1996–2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality.ResultsThe study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%.ConclusionsMedically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years – the group eligible for zoster vaccination – and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.     

Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan

BackgroundThe extended use of varicella vaccine in adults aged 50 and older against herpes zoster (HZ) was recently approved in Japan, which has raised the need to evaluate its value for money.MethodsWe conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of varicella vaccine immunisation programme for the elderly in Japan. Four strategies with different ages to receive a shot of vaccine were set, namely: (1) 65–84, (2) 70–84, (3) 75–84 and (4) 80–84 years old (y.o.). Incremental cost-effectiveness ratios (ICERs) compared with no programme from societal perspective were calculated. The health statuses following the target cohort are as follows: without any HZ-related disease, acute HZ followed by recovery, post-herpetic neuralgia (PHN) followed by recovery, post HZ/PHN, and general death. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Costs of per course of vaccination were assumed at ¥10,000 (US$91). The model with one-year cycle runs until the surviving individual reached 100 y.o.ResultsICERs ranged from ¥2,812,000/US$25,680 to ¥3,644,000/US$33,279 per QALY gained, with 65–84 y.o. strategy having the lowest ICER and 80–84 y.o. strategy the highest. None of the alternatives was strongly dominated by the other, while 80–84 y.o. and 70–84 y.o. strategy were extendedly dominated by 65–84 y.o. strategy. Probabilistic sensitivity analyses showed that the probabilities that ICER is under ¥5,000,000/US$45,662 per QALY gained was at 100% for 65–84 y.o., 70–84 y.o., 75–84 y.o. strategy, respectively, and at 98.4% for 80–84 y.o. strategy.ConclusionWe found that vaccinating individuals aged 65–84, 70–84, 75–84, and 80–84 with varicella vaccine to prevent HZ-associated disease in Japan can be cost-effective from societal perspective, with 65–84 y.o. strategy as the optimal alternative. Results are supported by one-way sensitivity analyses and probabilistic sensitivity analyses.     

The comparative efficacy and safety of herpes zoster vaccines: A network meta-analysis

BackgroundWe estimated the relative efficacy and safety of vaccines for prevention of herpes zoster (HZ) using network meta-analysis (NMA) based on evidence from randomized controlled trials.MethodsA systematic literature review evaluated two different HZ vaccines: adjuvanted recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL), with different formulations assessed. Detailed feasibility assessment indicated that a NMA was feasible for efficacy (incidence of HZ and postherpetic neuralgia [PHN]) and safety (serious adverse events [SAE] and reactogenicity [injection-site reactions, systemic reaction]) outcomes. Primary analyses included frequentist NMAs with fixed effects for efficacy outcomes, due to limited data availability, and both fixed and random effects for safety and reactogenicity outcomes. As age is a known effect modifier of vaccine efficacy (VE), VE analyses were stratified by age.ResultsRZV demonstrated significantly higher HZ efficacy than ZVL in adults ≥60 years of age (YOA) (VE_RZV = 0.92 (95% confidence interval [95%CI]: 0.88, 0.94), VE_ZVL = 0.51 (95%CI: 0.44, 0.57)) and adults ≥70 YOA (VE_RZV = 0.91 (95%CI: 0.87, 0.94), VE_ZVL = 0.37 (95%CI: 0.25, 0.48)). Similarly, RZV demonstrated significantly higher PHN efficacy than ZVL in adults ≥60 YOA (VE_RZV = 0.89 (95%CI: 0.70, 0.96), VE_ZVL = 0.66 (95%CI: 0.48, 0.78)) and adults ≥70 YOA (VE_RZV = 0.89 (95%CI: 0.69, 0.96), VE_ZVL = 0.67 (95%CI: 0.44, 0.80)). RZV was associated with significantly more injection-site and systemic reactions compared to most formulations of ZVL and placebo, however definitions and data collection procedures differed across the included studies. There were no statistically significant differences found between RZV and any formulation of ZVL or placebo for SAEs.ConclusionRZV is significantly more effective in reducing HZ and PHN incidence in adults ≥60 YOA, compared with ZVL. As anticipated with an adjuvanted vaccine, RZV results in more reactogenicity following immunization. No differences in SAEs were found between RZV and ZVL.     

Costs of herpes zoster complications in older adults: A cohort study of US claims database

Background/Objectives

Herpes zoster (HZ) incidence increases with age, and the burden of HZ is expected to grow with aging of populations worldwide. We aim to determine the incremental healthcare resource utilization and associated costs of patients with common HZ-related complications other than postherpetic neuralgia (cutaneous, neurologic and ophthalmic) compared to uncomplicated HZ.

The potential impact of increased recombinant zoster vaccine coverage on the burden of herpes zoster among adults aged 50–59 years

IntroductionRecombinant zoster vaccine (RZV) is recommended in the US for prevention of herpes zoster (HZ) in adults aged ≥50 years. Vaccination rates remain suboptimal for adults 50–59 years compared with adults ≥50 years overall. The objective of this study was to model changes in outcomes associated with improved RZV vaccination coverage in US adults 50–59 years.MethodsA multicohort Markov model compared a scenario using real-world vaccination coverage for US adults 50–59 years in 2020 versus scenarios assuming higher coverage. Outcomes, based on a lifetime horizon, included HZ cases and complications avoided, quality-adjusted life-years (QALY), and costs. Model inputs included HZ epidemiology, RZV vaccine efficacy, coverage, adverse events, and costs, based on published literature and US sources. Some inputs were updated from previous models, including real-world estimates of RZV coverage, series completion, and reflecting longer-term data on waning of vaccine efficacy. The model utilized a cohort size of 42,756,488 individuals based on the 2020 US population census.ResultsThe model projected that increasing RZV coverage in adults 50–59 years from 7.3 % to 14.6 % (to coverage for adults 60–64 years in 2020) would avoid an additional 504,468 HZ cases, 42,077 postherpetic neuralgia cases, and 56,247 cases of other HZ-associated complications. The increase in vaccine coverage would result in higher vaccination-related costs of $1,172,411,566, but the avoided HZ cases and complications would be expected to result in direct cost savings of $721,973,386 and indirect cost savings of $593,497,480 from avoided productivity loss. Overall, a gain of 5,230 discounted QALYs and cost savings of $143,059,299 from a societal perspective would be realized.ConclusionModestly higher RZV coverage in US adults 50–59 years could reduce the clinical burden associated with HZ and may result in societal cost savings. These findings demonstrate the potential value of increasing RZV vaccination in this population.     

Early antiviral treatment fails to completely prevent herpes-related pain

ObjectivesAntiviral therapy does not completely relieve herpes zoster (HZ)-related pain, including post-herpetic neuralgia (PHN). The 12-month longitudinal prospective observational ARIZONA study was conducted in primary care in France between November 20, 2006 and September 12, 2008. The ARIZONA study included data from 1358 patients 50 years of age or more, presenting with acute eruptive HZ. This article focuses on the relationship between antiviral therapy and HZ-related pain in this large population.Patients and methodsSix hundred and forty-four family physicians (FPs) consecutively included all patients 50 years of age or more presenting with acute HZ in the eruptive phase. The FP documented every patient's demographic and medical characteristics, HZ characteristics, and prescribed drugs at inclusion, and the presence of HZ-related pain on day 15 and at months 1, 3, 6, 9, and 12.ResultsOne thousand two hundred and fifty-eight (92.6%) of the 1358 included patients (mean 67.7 years [SD 10.7]; 62.2% female patients) were given antiviral drugs. The prevalence of HZ-related pain was 43.6%, 27.0%, 11.7%, 8.7%, 7.4%, and 6.0%, on day 15 and at months 1, 3, 6, 9, and 12, respectively. HZ-related pain was at least as frequent in patients treated by antiviral therapy within 72 hours following HZ-rash onset as in patients treated later or who did not receive antiviral treatment, and more frequent in patients whose diagnosis was made within 24 hours following HZ-rash onset.ConclusionsAntiviral therapy, even early, does not prevent HZ-related pain and PHN, probably because patients quickly identified and treated were those with severe forms and potentially at high risk of pain. Preventive strategies are thus needed.     

Potential cost-effectiveness of adjuvanted herpes zoster subunit vaccine for older adults in Hong Kong

BackgroundAdjuvanted herpes zoster (HZ) subunit vaccine is recommended for adults aged ≥50 years. This study aimed to investigate cost-effectiveness of HZ subunit vaccine for older adults at different age in Hong Kong.MethodsA life-long Markov model was designed to simulate outcomes of four alternatives: Vaccination at model entry (age 50 years); deferring vaccination to 60 years; deferring vaccination to 70 years; and no vaccination. Outcome measures included direct cost, indirect cost, HZ and post-herpetic neuralgia incidences, quality-adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER). Model clinical inputs were derived from literature. HZ treatment costs were collected from a cohort of HZ patients (n = 218). One-way and probabilistic sensitivity analyses were performed.ResultsIn base-case analysis, vaccination at 50 years showed highest QALYs saved and increment cost (0.00258; USD166), followed by deferring to 60 years (0.00215 QALYs saved; USD102) and deferring to 70 years (0.00134 QALYs; USD62) when comparing to no vaccination. ICERs of vaccination arms versus no vaccine (46,267–64,341 USD/QALY) were between 1–3 × gross domestic product (GPD) per capita in Hong Kong (USD43,530–USD130,590). One-way sensitivity analyses found vaccine cost to be the common and most influential parameter for ICER of each vaccination strategy to become <1 × GDP per capita. In probabilistic sensitivity analysis, vaccination at 50 years, deferring to 60 years and 70 years were accepted as cost-effective in 90% of time at willingness-to-pay (WTP) of 78,400 USD/QALY, 57,680 USD/QALY and 53,760 USD/QALY, respectively.ConclusionsCost-effectiveness of each strategy is highly subject to the vaccine cost and WTP threshold per QALY saved.     

Safety,tolerability, and immunogenicity of zoster vaccine in subjects on chronic/maintenance corticosteroids

BackgroundThis randomized, placebo-controlled study assessed the safety, tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals receiving chronic/maintenance systemic corticosteroid therapy (daily dose equivalent of 5–20 mg prednisone) for ≥2 weeks prior to vaccination and ≥6 weeks postvaccination.MethodsSubjects were followed for adverse experiences (AEs), exposure to varicella or herpes zoster (HZ), or development of varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination (primary safety follow-up period) and for serious AEs (SAEs) through Day 182 postvaccination (secondary follow-up period). Varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and at Week 6 postvaccination.ResultsThe proportions of subjects reporting systemic AEs and SAEs were similar in both groups. A higher percentage of subjects reported injection-site AEs in the ZV group (21.5%) than in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16 postvaccination) was reported in the ZV group and deemed vaccine-related by the study investigator; however, PCR testing confirmed the presence of wild-type (not vaccine strain) VZV.Geometric mean titer (GMT) at 6 weeks postvaccination was higher for ZV recipients than placebo recipients, with estimated geometric mean fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully.ConclusionsIn adults ≥60 years old on chronic/maintenance corticosteroids, ZV was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks postvaccination were higher in the ZV group than in the placebo group.     

Incidences of Herpes Zoster and Postherpetic Neuralgia in Japanese Adults Aged 50 Years and Older From a Community-based Prospective Cohort Study: The SHEZ Study

Background

Many cross-sectional studies have examined the incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN), but prospective studies in Japanese older adults are lacking. Therefore, we conducted a community-based prospective cohort study to determine the incidence in Japanese adults aged ≥50 years.

Methods

We recruited 12 522 participants from Shozu County, Kagawa Prefecture, between December 2008 and November 2009 and followed participants for 3 years. When a subject presented with symptoms suggestive of HZ, they were examined at collaborating medical institutions and cooperated with onset and recovery surveys (eg, measurement of varicella zoster virus-specific immunity and a pain survey). The hazard ratios (HRs) of HZ and PHN according to sex and age were analyzed by Cox regression analysis with a significance level of 5%.

Results

The incidence of HZ was 10.9/1000 person-years (men: 8.5/1000 person-years; women: 12.8/1000 person-years) and was significantly higher in women than in men (HR 1.5; 95% confidence interval, 1.2–1.8). The incidence of PHN was 2.1/1000 person-years (men: 1.7/1000 person-years; women: 2.4/1000 person-years), with no significant sex differences. A total of 19% of HZ cases progressed to PHN; no sex-specific difference in the proportion of PHN cases was observed.

Conclusions

We clarified the accurate incidences of HZ and PHN in a population of Japanese older adults. These incidences increased with age. HZ incidence was higher in women than in men, while PHN incidence did not differ markedly between the sexes.Key words: herpes zoster, postherpetic neuralgia, incidence, prospective cohort study, Japanese adults     

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years

ObjectivesThis study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices.MethodsHematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses.ResultsBase-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions.ConclusionsGenerally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.     

Cost-effectiveness of Recombinant Zoster Vaccine (RZV) and Varicella Vaccine Live (VVL) against herpes zoster and post-herpetic neuralgia among adults aged 65 and over in Japan

BackgroundThe approval of the extended use of 1-dose varicella vaccine (VVL) in adults aged 50 and older against herpes zoster (HZ) in 2016 and the 2-dose recombinant zoster vaccine (RZV) in 2018 raised the need to evaluate the value for money between these two vaccines.MethodsWe conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of the immunisation programmes from payer’s perspective. Eight strategies with different ages to receive VVL or RZV were set, namely: 65–84 year old (y.o.), 70–84 y.o., 75–84 y.o., and 80–84 y.o. VVL- or RZV-strategy. Incremental cost-effectiveness ratios (ICERs) compared with curative care scenario were calculated. The health statuses following the target cohort were as follows: acute HZ followed by recovery, post-herpetic neuralgia followed by recovery, post HZ/PHN, recurrence of HZ, and general death.ResultsAt the vaccination cost ¥8000 (US$73) for 1-dose ZVL and ¥30,000 (US$273) for 2-dose RZV, ICERs ranged from ¥2,633,587/US$23,942 (age 80–84 y.o.) to ¥3,434,267 or US$31,221 (age 65–84 y.o.)/QALY gained for VVL-strategies; from ¥5,262,227 or US$47,838 (age 80–84 y.o.) to ¥6,278,557 or US$57,078/QALY gained (age 65–84 y.o.) for RZV-strategies. Cost-effectiveness acceptability curves derived from probabilistic sensitivity analyses showed that if the cost-effective threshold was at ¥3,000,000 or US$27,273/QALY, the acceptability was 90.7% and 8.8% for 65–84 VVL-strategy and 65–84 RZV-strategy, respectively; if at ¥5,000,000 or US$45,455/QALY, 56.2% and 43.8%, and if at ¥10,000,000 or US$90,909/QALY 11.9% and 88.1%, respectively.ConclusionVaccinating individuals aged 65–84 y.o., 70–84 y.o., 75–84 y.o., 80–84 y.o. with VVL or RZV to prevent HZ-associated disease in Japan can be cost-effective from payer’s perspective, with vaccination costs at ¥8,000 per shot for VVL, ¥30,000 for 2-dose RZV. While the results suggesting that only 65–84 VVL-strategy and 65–84 RZV strategy should be considered when introducing HZ immunisation programme. The optimal strategy varies depending on the willingness-to-pay threshold.     

Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults

BackgroundAn investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01_B adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25 μg, 50 μg, or 100 μg gE) was conducted in adults ≥60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50 μg gE/AS01_B formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination.MethodsThis phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4⁺ T cells expressing ≥2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose.ResultsSix years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20–25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4⁺ T cells per 10⁶ cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3 mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72.ConclusionsgE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.     

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention

BackgroundPostherpetic neuralgia (PHN) occurs in 5–30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN.MethodsWe conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status.ResultsFrom 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent.ConclusionsOverall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.     

The impact of herpes zoster and post-herpetic neuralgia on quality of life: patient-reported outcomes in six European countries

AIM: To investigate the impact of an entire episode of herpes zoster (HZ) or post-herpetic neuralgia (PHN) on an individual's quality of life (QoL). SUBJECTS AND METHODS: Individuals aged ≥50?years with painful HZ in the previous 5?years were identified across six European countries (Spain, Portugal, The Netherlands, Belgium, Sweden and Switzerland). They participated in a survey comprising bespoke questions to evaluate their previous HZ/PHN episode. RESULTS: A total of 1,005 individuals participated, 874 (87%) having had HZ, and 13% having had PHN. Generally, pain and QoL outcomes were similar irrespective of when HZ was diagnosed (≤12 versus 13-60?months) and age (50-59 versus ≥60?years). Mean pain scores were significantly higher in those with PHN versus HZ both on average (7.2 versus 6.4) and at worst (8.3 versus 7.4). PHN had a significantly higher impact on patients' perception of their overall QoL, with 37% reporting a high impact (HZ: 19%). Pain restrictions in the following QoL domains significantly impacted on the respondents' perception of QoL: enjoyment of life (level of impact, 31%), general activity (29%), mood (25%), sleep (8%) and walking ability (8%), and were significantly higher in those with PHN than in those with HZ. Sleep was the area worst affected. CONCLUSION: HZ, and particularly PHN, is associated with considerable levels of pain that have a significant impact on the QoL of participants across six European countries.