Recombinant zoster vaccine coverage in the United States: An analysis of claims-based data

Recombinant zoster vaccine (RZV) is recommended for individuals ≥ 50 years of age for protection against herpes zoster (HZ). This study quantifies RZV coverage and assesses predictors for RZV vaccination using a U.S. claims database. Univariate linear regression provided annual prevalence of RZV vaccination and multivariable logistic regression provided ORs and 95% CIs for associations between predictors and RZV vaccination. A total of 4,124,315 individuals (19,080,914 person-years) were included in this study. Since receiving FDA approval for the prevention of HZ, RZV coverage (of at least one dose) has reached approximately 17% within the eligible U.S. population by January 2021, although significant disparities between demographic groups were noted. Our findings suggest that HZ vaccine coverage may be reduced below goal in the U.S. and highlights the importance of continuing to monitor RZV vaccination. Additionally, as our study found disparities in vaccine coverage, attention towards marginalized and medically underserved populations is needed.     

Effectiveness of recombinant zoster vaccine (RZV) in patients with inflammatory bowel disease

Background and AimsPatients with Inflammatory bowel disease (IBD) are at an increased risk of developing herpes zoster (HZ). The effectiveness of the recombinant zoster vaccine (RZV) in patients with IBD is unknown.MethodsIn this retrospective cohort study using Explorys (October 2017–April 2020; IBM Corporation, Somers, NY, USA), the effectiveness of RZV for the prevention of HZ in patients with IBD ≥ 50 years was compared to general population aged ≥ 50 years. Rates of de-novo HZ were compared between patients with IBD and the general population and stratified by number of RZV doses received. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).ResultsThe overall proportion of IBD patients ≥ 50 years who received HZ vaccination with the live zoster vaccine (ZVL) or RZV was low (n = 11320, out of 112,200 IBD patients in the cohort). A total of 1670 patients received RZV. Receipt of the RZV resulted in a significantly lower rate of HZ in IBD patients (OR 0.36, 95% CI 0.23–0.56) compared to the general population (OR 0.74, 95% CI 0.59–0.92). However, despite vaccination, patients with IBD who received the RZV were still 3-times more likely to develop HZ during the study follow up period compared to the general population receiving the RZV (OR 3.06, 95% CI 1.87–5.02) and unvaccinated IBD patients were 6-times more likely to develop HZ compared to general population (OR 6.21, 95% CI 6.02–6.41).ConclusionThe recombinant zoster vaccine is effective in reducing the risk of HZ in patients with IBD compared to the general population. During our follow up period, patients with IBD, however, still remain at an increased risk for HZ despite vaccination.     

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.     

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.     

Evaluation of the incidence of herpes zoster after concomitant administration of zoster vaccine and polysaccharide pneumococcal vaccine

In 2009, a revision to the zoster vaccine package insert was approved stating that the zoster vaccine and the pneumococcal vaccine should not be given concurrently because concomitant use resulted in reduced immunogenicity of the zoster vaccine. We conducted an observational study to evaluate if concomitant vaccination reduces the protective effect of the zoster vaccine. The study was conducted in Kaiser Permanente Southern California. Incidence of herpes zoster (HZ) after vaccination with a zoster vaccine in the population receiving both vaccines on the same day was compared to that in the population receiving a pneumococcal vaccine within one year to 30 days prior to zoster vaccine. Vaccinations and incident HZ cases were identified by electronic health records. The hazard ratio for incident HZ associated with concomitant vs. nonconcomitant vaccination was estimated using the Cox proportional hazard model. There were 56 incident HZ cases in the concomitant vaccination cohort and 58 in the nonconcomitant vaccination cohort, yielding a HZ incidence of 4.54 (95% confidence interval [CI], 3.43-5.89) and 4.51 (95% CI, 3.42-5.83) per 1000 person-years, respectively. The hazard ratio comparing the incidence rate of HZ in the two cohorts was 1.19 (95% CI, 0.81-1.74) in the adjusted analysis. In this study, we found no evidence of an increased risk of HZ in the population receiving zoster vaccine and pneumococcal vaccine concomitantly. The revision of the product information needs to be carefully assessed to avoid introducing barriers to patients and providers who are interested in these two important vaccines.     

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.     

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.     

Ten years of experience with herpes zoster vaccine in primary care- how attitudes and practices have changed and what it may mean for a new zoster vaccine

Zoster vaccine live (ZVL [Zostavax]) has been recommended for the prevention of herpes zoster (HZ) among immunocompetent adults ≥60 years in the United States since 2008. To examine changes in healthcare providers’ perceptions and practices related to HZ disease and vaccination, we administered surveys to national networks of primary care physicians in 2005, 2008, and 2016. Ten years after ZVL was first licensed, physicians were more likely to respond that they perceived HZ as a serious disease and more strongly recommended ZVL, and were less likely to report less likely to report several major barriers to HZ vaccination such as patient cost, vaccine effectiveness and competing medical concerns. Overall, physician attitudes appear to be more favorable towards zoster vaccination after a decade of availability of a HZ vaccine. The new recombinant zoster vaccine (RZV [Shingrix]) may benefit from physician’s increased perception of the importance of HZ and HZ vaccination.     

Effectiveness of herpes zoster vaccination in an older United Kingdom population

BackgroundVaccination against herpes zoster was introduced in the United Kingdom in 2013 for individuals aged 70 years, with a phased catch-up campaign for 71–79 year olds. Vaccine introduction has resulted in a marked fall in incident herpes zoster and in post-herpetic neuralgia (PHN), but formal evaluation of vaccine effectiveness is needed.MethodsIn a population-based cohort study of older individuals born between 1933 and 1946, we used linked UK anonymised primary care health records for the first three years of the vaccination programme (01/09/2013–31/08/2016) and multivariable Poisson regression to obtain incidence rates and vaccine effectiveness (VE) against zoster and PHN.ResultsAmong 516,547 individuals, 21% were vaccinated. Incidence of zoster was 3.15/1000 person-years in vaccinees and 8.80/1000 person-years in unvaccinated individuals. After adjustment, VE was 64% (95%CI = 60–68%) against incident zoster and 81% (95%CI = 61–91%) against PHN, with very similar VE estimates in the routine and catch-up cohorts. VE against zoster was lower in those with a previous history of zoster: 47% (95%CI = 31–58%) versus 64% (95%CI = 60–68%) in those without previous zoster. There was evidence of waning VE over time, from 69% (95%CI = 65–74%) in the first year after vaccination to 45% (95%CI = 29–57%) by the third year.ConclusionThis first formal assessment of VE in the UK zoster vaccination programme demonstrates good effectiveness of zoster vaccine, and very good protection against PHN. The findings provide evidence that VE is similar across the age groups targeted for vaccination in the UK, and on duration of protection of the vaccine in public health use. The study provides key information for decision-makers about the future direction of UK zoster vaccination programme, indicating that the live zoster vaccine may be more cost-effective than estimated previously. It also supports efforts to communicate the benefits of zoster vaccination to address the declining coverage observed across the UK.     

Effectiveness of the herpes zoster vaccine Zostavax® in Stockholm County,Sweden

ObjectiveThe objective of this study was to estimate the effectiveness of the herpes zoster vaccine Zostavax in a cohort of vaccinated individuals in Sweden.MethodsThe study is a retrospective population-based matched cohort study conducted with data from health care registers in Stockholm Country. Primary endpoints were new diagnosis of HZ after administration of Zostavax. Individuals above the age of 50 years and living in Stockholm County in 2013 were included into the study. Ten non-vaccinated individuals per vaccinated were included and randomized into the cohort. The non-vaccinated were matched on age at index date and gender.ResultsZostavax had an overall effectiveness (VE) of 34% (HR = 0.66, 95% CI: 0.55–0.78). When stratifying by age, 61–75 years was the only age group that showed a reduced risk of HZ (HR = 0.57; CI 0.44–0.73) compared to those that were non-vaccinated. As compared to the unvaccinated group, the VE was significant at days 180–359 (HR = 0.53; 95% CI 0.33–0.88), 360–539 (HR = 0.46; 95% CI 0.27–0.80) and at days 540–719 (HR = 0.56; 95% CI 0.35–0.90) after vaccination.ConclusionThis is the first population-based study in Sweden studying the effectiveness of HZ vaccination. Our findings are well in-line with previous studies, however studies addressing the longitudinal efficacy and effectiveness of Zostavax are still required.     

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.     

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.     

Review of the initial post-marketing safety surveillance for the recombinant zoster vaccine

BackgroundThe adjuvanted recombinant zoster vaccine (RZV) received its first marketing authorization in October 2017, for prevention of herpes zoster in individuals aged ≥50 years.MethodsWe summarized safety information, following RZV administration, received by GSK via spontaneous adverse event (AE) reports submitted by healthcare providers, vaccine recipients and other reporters. Observed-to-expected (O/E) analyses were performed for selected outcomes: reports of death, Guillain–Barré syndrome and Bell’s palsy. Standard case definitions were used to assess individual case reports. Data mining, using proportional reporting ratio and time-to-onset signal detection methods, was employed to identify RZV-AE pairs with disproportionate reporting or unexpected time-to-onset distribution.ResultsBetween October 13, 2017 and February 10, 2019, an estimated 9.3 million doses were distributed and GSK received 15,638 spontaneous AE reports involving RZV. Most reports were classified as non-serious (95.3%) and originated from the United States (81.7%), where the majority of doses were distributed. Among reports with age or sex reported, individuals were mainly 50–69-year-olds (62.1%) and female (66.7%). Of all reports, 3,579 (22.9%) described vaccination errors, of which 82.7% were without associated symptoms. Of all vaccination error reports, most described errors of vaccine preparation and reconstitution (29.7%), inappropriate schedule or incomplete course of administration (26.7%), incorrect route of administration (16.4%), and storage errors (12.9%). The most commonly reported symptoms were consistent with the known RZV reactogenicity profile observed in clinical trials, including injection site reactions, pyrexia, chills, fatigue, headache. O/E analyses for selected outcomes and data mining analyses for all reported AEs did not identify any unexpected patterns.ConclusionsReview of the initial data from the post-marketing safety surveillance showed that the safety profile of RZV is consistent with that previously observed in pre-licensure clinical trials. Other studies are ongoing and planned, to continue generating real-world safety data and further characterize RZV.     

Predictors of herpes zoster vaccination among Australian adults aged 65 and over

Objective(s)To estimate HZ vaccine coverage in Australia among older Australians and to identify potential barriers to vaccination.DesignAnalysis of data from three cross-sectional surveys administered online between 2019 and 2020.Setting and participantsAdults aged 65 and over residing in Australia.Main outcome measuresSelf-reported herpes zoster vaccination.ResultsAmong the 744 adults aged 65 and over in this sample, 32% reported being vaccinated for HZ, including 23% of participants aged 65–74, 55% of participants aged 75–84, and 0% for participants aged 85 and above. Those who are vaccinated with other immunisations are more likely to have received HZ vaccine, including seasonal influenza (OR = 4.41, 95 % CI: 2.44–7.98) and pneumococcal vaccines (OR = 4.43, 95 % CI: 2.92 – 6.75). Participants with a history of certain conditions, such as stroke (OR = 2.26, 95 % CI: 1.13–4.49), were more likely to be vaccinated against HZ. Participants that reported smoking tobacco daily were less likely to be vaccinated against HZ (OR = 0.48, 95 % CI: 0.26–0.89). Participants were less likely to be vaccinated against HZ if they preferred to develop immunity ‘naturally’ (OR = 0.29, 95 % CI: 0.15 – 0.57) or expressed distrust of vaccines (OR = 0.34, 95 % CI: 0.13–0.91).Conclusion(s)Further research is required to understand the barriers to HZ vaccine uptake. Increasing the funding eligibility for those who are at risk of complications from shingles, or lowering the age of eligibility, may increase vaccine coverage.     

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine co-administered with the 23-valent pneumococcal polysaccharide vaccine in adults ≥50 years of age: A randomized trial

BackgroundThis study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) when the first dose was co-administered with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults aged ≥50 years.MethodsIn this open label, multi-center study (NCT02045836), participants were randomized 1:1 to receive either the first dose of RZV and PPSV23, co-administered at Day 0 and the second dose of RZV at Month 2 (Co-Ad group), or PPSV23 at Day 0, the first dose of RZV at Month 2 and second dose of RZV at Month 4 (Control group). Co-primary objectives were the RZV vaccine response rate (VRR) in the Co-Ad group and the non-inferiority of the antibody responses to RZV and PPSV23 in the Co-Ad group compared to the Control group. Reactogenicity and safety were also assessed.Results865 participants were vaccinated (Co-Ad: 432, Control: 433). VRRs to RZV were >98% in both groups. Humoral immune responses to co-administration of RZV and PPSV23 were non-inferior to sequential administration. All three co-primary immunogenicity objectives were met. Solicited local symptoms after the first RZV dose were reported by similar percentages of participants in both groups. Solicited general symptoms were more frequently reported when the first dose of RZV and PPSV23 were co-administered. No differences were apparent between groups after the second RZV dose.ConclusionsNo immunologic interference was observed between RZV and PPSV23 when co-administered in adults ≥50 years. No safety concerns were raised.     

Recombinant zoster vaccine (RZV) second-dose series completion in adults aged 50–64 years in the United States

In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥ 50 years, with the 2nd dose recommended 2–6 months after the 1st dose. We estimated second-dose RZV series completion in the U.S. among 50–64-year-olds using two administrative databases. Second-dose RZV series completion was ～70% within 6-months and 80% within 12-months of first dose. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 96% had a missed opportunity for a second-dose vaccination, defined as a provider or pharmacy visit, among whom 36% had a visit for influenza or pneumococcal vaccination within 2–12 months of their first-dose of RZV. We found that RZV series completion rates in 50–64-year-olds was high. Availability of RZV at pharmacies has potentially helped increase series completion, but missed opportunities remain.     

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.     

Safety,tolerability, and immunogenicity of zoster vaccine in subjects with a history of herpes zoster

Background

Prior clinical studies of zoster vaccine enrolled subjects without a history of herpes zoster (HZ), so there are limited data on safety and immunogenicity in vaccinees with a prior history of HZ. This study was conducted to evaluate the safety and immunogenicity of zoster vaccine recipients who had a prior episode of HZ.

Methods

A total of 101 subjects ≥50 years of age with a prior history of HZ were enrolled. They were stratified by number of years since their HZ (5 to 9 years and ≥10 years, in an approximate 2:1 ratio), and randomized 1:1 to one of two vaccination groups. On day 1, Group I was administered zoster vaccine and Group II received placebo. At week 4, Group I received placebo and Group II received zoster vaccine. Subjects were followed for adverse experiences (AEs), exposure to varicella or HZ, and development of any varicella/varicella-like or HZ/HZ-like rashes, for 28 days after each injection. Blood samples were obtained prior to study injection on day 1 and week 4, and at week 8. Serum was assessed for varicella-zoster virus (VZV) antibody concentration by glycoprotein enzyme-linked immunosorbent assay.

Results

No serious AEs were reported within the 28-day safety follow-up period following any vaccination. Although a higher percentage of subjects reported injection-site AEs after receiving zoster vaccine than did placebo recipients, the proportion of subjects reporting systemic clinical AEs was similar in both groups. Zoster vaccine induced a VZV antibody response at 4 weeks post-vaccination. The estimated geometric mean titer (GMT) ratio (vaccine/placebo) was 2.07 (95% CI: 1.48, 2.88). The geometric mean fold-rise (GMFR) from prevaccination to week 4 post-vaccination was 2.1 in zoster vaccine recipients, versus 1.0 in placebo recipients.

Conclusions

In HZ history-positive adults ≥50 years of age, zoster vaccine: (1) was well tolerated; and (2) significantly boosted the level of VZV antibody from baseline to 4 weeks post-vaccination as measured by GMT and GMFR. These data support the Advisory Committee on Immunization Practices’ recommendation for routine zoster vaccination for all immunocompetent persons ≥60 years of age irrespective of HZ history.     

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.