Burden-of-illness vaccine efficacy.

In recent years, many vaccines have been developed for the prevention of a variety of diseases. Although the primary objective of vaccination is to prevent disease, vaccination can also reduce the severity of disease in those individuals who develop breakthrough disease. Observations of apparent mitigation of breakthrough disease in vaccine recipients have been reported for a number of vaccine-preventable diseases such as Herpes Zoster, Influenza, Rotavirus, and Pertussis. The burden-of-illness (BOI) score was developed to incorporate the incidence of disease as well as the severity and duration of disease. A severity-of-illness score S > 0 is assigned to individuals who develop disease and a score of 0 is assigned to uninfected individuals. In this article, we derive the vaccine efficacy statistic (which is the standard statistic for presenting efficacy outcomes in vaccine clinical trials) based on BOI scores, and we extend the method to adjust for baseline covariates. Also, we illustrate it with data from a clinical trial in which the efficacy of a Herpes Zoster vaccine was evaluated.

Recombinant Zoster Vaccine Significantly Reduces the Impact on Quality of Life Caused by Herpes Zoster in Adult Autologous Hematopoietic Stem Cell Transplant Recipients: A Randomized Placebo-Controlled Trial (ZOE-HSCT).

Herpes zoster (HZ) can have a substantial impact on quality of life (QoL). The vaccine efficacy (VE) of a recombinant zoster vaccine (RZV) was 68.2% (95% confidence interval [CI], 55.6% to 77.5%) in a phase 3 study in adult autologous hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). Herein, we report the impact of RZV on patients' QoL. Autologous HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1 to 2 months apart. QoL was measured by the Short Form Survey-36 and Euro-QoL-5 Dimension at baseline, 1 month, and 1 year postdose 2 and during suspected HZ episodes with the Zoster Brief Pain Inventory (ZBPI). The RZV impact on ZBPI burden of illness and burden of interference scores was estimated. The 2 scores were calculated from the area under the curve (days 0 to 182) of the ZBPI worst pain and ZBPI activities of daily living scores, respectively, assuming a score of 0 for patients not having a confirmed HZ episode. The ZBPI maximum worst pain score was significantly lower in the RZV than placebo group (mean: 5.8 versus 7.1, P = .011). Consequently, the VE estimates for HZ burden of illness (82.5%; 95% CI, 73.6 to 91.4) and burden of interference (82.8%; 95% CI, 73.3 to 92.3) were higher than the HZ VE estimate (ie, 68.2%). RZV showed significantly better QoL scores than placebo 1 week following rash onset among patients with confirmed HZ. In addition to reducing the risk of HZ and its complications, RZV significantly reduced the impact of HZ on patients' QoL in those who developed breakthrough disease.

Impact of herpes zoster and postherpetic neuralgia on the quality of life of Germans aged 50 or above.

BACKGROUND: Herpes zoster (HZ) is a painful dermatomal rash caused by reactivation of latent varicella zoster virus surviving in the patient's sensory ganglia after a previous episode of varicella. The incidence of HZ increases markedly with age as does the proportion of HZ patients who develop postherpetic neuralgia (PHN) with often severe and debilitating pain persisting for months and even years. This prospective study aimed to assess the impact of HZ and PHN on the quality of life (QoL) of individuals aged ≥ 50 years in Germany. METHODS: Patients were recruited when consulting primary care physicians for a first HZ episode. PHN was defined as a 'worst' pain score ≥ 3 on the Zoster Brief Pain Inventory (ZBPI) scale persisting or appearing 90 days or more after rash onset. PHN-cases were followed for up to nine months after rash onset. The interference of pain with patients' ability to carry out normal activities was assessed by the ZBPI activities of daily living (ADL) scale and QoL by the EuroQoL five-dimension scale (EQ-5D) utility score. RESULTS: Of 513 patients enrolled, 61 (11.9%) developed PHN. At HZ onset, the mean ZBPI worst pain score of all patients was 5.1, the least square (LS)means estimates of the ZBPI ADL and EQ-5D utility scores were 2.970 and 0.740, respectively. Over three months follow-up, the pain scores decreased and the QoL increased monotonically across all age groups. At Day 90, the mean ZBPI worst pain score of the PHN patients was 4.4, while the LSmeans estimates of the ZBPI ADL and EQ-5D utility scores were 2.899 and 0.826, respectively. For patients with PHN persisting at nine months, the pain scores and QoL remained unchanged over the six months following the development of PHN. CONCLUSION: HZ and PHN had a substantial impact on the patients' QoL and ability to function in their normal activities. There was a clear association in time between the evolution of pain and estimated QoL. The impact on ADL and QoL did not vary with age.

The temporal impact of aging on the burden of herpes zoster.

BACKGROUND: The risk of Herpes Zoster (HZ) increases with age and various studies have also demonstrated an increasing HZ incidence globally. Simultaneously, the global trend of an aging population has placed a greater burden on the healthcare system. This study aims to estimate the potential burden of HZ over time accounting for the increasing trends of both HZ incidence and global aging. METHODS: A recent systematic review on HZ incidence identified studies that evaluated the temporal effects of HZ incidence. Data from the identified studies were extracted to estimate the trend of HZ incidence in the ≥65-year-old age cohort. The incidence rates were estimated up to the year 2030 using two scenarios: a linear extrapolation and a last observation carried forward. Three countries were chosen to perform the analysis on: Australia, Japan and the United States. RESULTS: The incidence data from the three countries showed an average annual increase between 2.35 and 3.74% over the time period of the studies selected. The elderly population for the US, Japan and Australia are expected to increase by 55, 10 and 53% respectively by the year 2030 compared to the levels in 2015. Under the first scenario between 2001 and 2030, the number of annual incident cases of HZ in those aged ≥65 years is expected to increase by +343% (293,785 to 1,303,328), +176% (158,616 to 437,867) and +376% (18,105 to 86,268) in the US, Japan and Australia respectively while those for the second scenario are +150%, +83% and +223% respectively. In the US alone, the estimated annual cost of HZ-related cases in the ≥65 age cohort is approximately 4.74 Billion US$ in 2030. CONCLUSIONS: The increasing incidence of HZ coupled with the demographic trends (i.e., aging population and greater life expectancy) in many countries are likely to imply a rising economic burden of HZ on already constrained healthcare budgets.

Budget constraint and vaccine dosing: a mathematical modelling exercise.

BACKGROUND: Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective. METHODS: An optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example. RESULTS: With a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ≥5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development. CONCLUSIONS: Under budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.

Differential Utility Losses in Herpes Zoster Cases Between Vaccinated and Unvaccinated Subjects: A Meta-analysis of Three Clinical Trials.

BACKGROUND AND OBJECTIVE: Recombinant zoster vaccine (RZV) is approved in adults for the prevention of herpes zoster. The effect of RZV in moderating the severity of breakthrough cases of herpes zoster has been noted but not explicitly quantified before. In this study, a meta-analysis was undertaken to estimate differential utility losses between unvaccinated (Placebo) and vaccinated (RZV) subjects in breakthrough cases of herpes zoster from three RZV clinical trials. METHODS: Differential utility losses between the two groups were estimated in units of quality-adjusted life-years (QALYs), leveraging aggregate patient data from the ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) clinical trials. Differential utility losses and the ratio of mean utility losses were analyzed using random-effects and fixed-effects meta-regression models. RESULTS: The mean QALY loss differences between the unvaccinated (Placebo) and vaccinated (RZV) groups were 0.008, 0.004, and 0.011 in the ZOE-50, ZOE-70, and ZOE-HSCT studies, respectively, yielding an overall estimated difference of 0.007 (95% confidence interval 0.002-0.012) QALYs. Quality-adjusted life-year loss in the vaccinated group was estimated to be 35.5% of the value in the placebo group. A sensitivity analysis estimated an overall difference of 0.005 (95% confidence interval 0.001-0.009) QALYs, corresponding to 48.6% of the QALY loss value in the placebo group. CONCLUSIONS: Recombinant zoster vaccine is effective in alleviating disease severity in breakthrough cases of herpes zoster. The results may be useful in distinguishing QALY losses between vaccinated and unvaccinated cohorts in health economics studies, particularly cost-effectiveness analyses.

Herpes zoster, also known as shingles, may cause painful rashes and persistent pain for months or even years after the initial episode. Recombinant zoster vaccine is approved for the prevention of shingles. Pivotal recombinant zoster vaccine clinical trials have reported data about the impact of shingles episodes on daily activities and overall health-related quality of life. In this work, we combined data from three recombinant zoster vaccine clinical trials and compared the loss in quality of life­measured in quality-adjusted life-years­incurred by vaccinated and unvaccinated subjects who experienced a shingles episode. We found that vaccinated patients experienced lower quality-adjusted life-year losses when they developed shingles compared with unvaccinated patients. Our results may be useful in assessing quality-adjusted life-year losses between vaccinated and unvaccinated cohorts in future herpes zoster vaccination health economics analyses.

The Impact of the COVID-19 Pandemic on the Incidence of Herpes Zoster: A Narrative Literature Review.

Coronavirus disease 2019 (COVID-19) has had a broad impact on health services and health outcomes. During the pandemic, there were numerous reports of herpes zoster (HZ) in people with COVID-19 and in COVID-19 vaccine recipients. The aim of this review is to elucidate the global effects of the COVID-19 pandemic on HZ. It is postulated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces an immunosuppressive state that favours varicella zoster virus (VZV) reactivation. Three large cohort studies (a multinational study and studies from the USA and Spain) that excluded individuals vaccinated against HZ reported significantly increased risk of HZ following COVID-19 infection, especially in people aged ≥ 50 years. In contrast, a large study from Israel that did not consider HZ vaccination status reported no such increase. Cases of HZ following COVID-19 vaccination have been reported and may be the result of attenuated cell-mediated immunity. This phenomenon appears to vary by vaccine type. Some (but not all) large analyses have reported a significant positive relationship between receipt of mRNA vaccines for COVID-19 and development of HZ. These include analyses of health records databases in Israel and Hong Kong and of spontaneous case reports in the US Vaccine Adverse Event Reporting System (VAERS) database. Routine vaccinations, including shingles vaccine programmes, were disrupted by the COVID-19 pandemic. It is estimated that missed shingles vaccinations may have resulted in 63,117 avoidable HZ cases in the USA. Now that the World Health Organization has declared an end to the COVID-19 pandemic as a health emergency and routine vaccination services have resumed, there is a need to increase awareness of HZ and HZ vaccination.Graphical abstract available for this article.

Herpes zoster in older adults: Impact on carbon footprint in the United States.

We provide estimates for (I) annual herpes zoster (HZ) cases, (II) carbon costs related to healthcare utilization, and (III) annual carbon emissions due to HZ among ≥50 years of age (YOA) United States (US) population. We estimated the annual number of HZ cases in the US based on available incidence data and demographic data of individuals ≥50 YOA. Both the healthcare resource utilization (HCRU) associated with HZ cases and the unit carbon dioxide equivalent (i.e. CO2e) costs associated with each type of HCRU in the US were estimated based on literature and studies available online. The carbon footprint associated with HZ annually among US adults ≥50 YOA was estimated by multiplying the unit carbon estimates by the HCRU. In the US population aged ≥50 YOA in 2020 (i.e. approximately 118 million), approximately 1.1 million cases of HZ occur annually assuming no vaccination. Based on 2 sources of HCRU the average kgCO2e per HZ patient ranged from 61.0 to 97.6 kgCO2e, with values by age group ranging from 40.9 kgCO2e in patients aged 50-59 to 195.9 kgCO2e in patients ≥80 YOA. The total annual HZ associated carbon ranged between 67,000 and 107,000 tons of CO2e in the US population aged ≥50 YOA. The impact of HZ on carbon footprint in the US results in considerable greenhouse gas (GHG)emissions. Assuming no vaccination, the burden of HZ is projected to rise over the coming years with the aging populations consequently worsening its impact on GHG emissions. (Figure 1).

The Incidence of Herpes Zoster Complications: A Systematic Literature Review.

INTRODUCTION: The objective of this work was to summarize the incidence of herpes zoster (HZ) complications in different populations. METHODS: Systematic literature review of PubMed, Embase, and Virtual Health Library records between January 1, 2002 and October 20, 2022 using search strings for HZ, complications, and frequency measurements. RESULTS: The review included 124 studies, most conducted in the general population (n = 93) and on individuals with comorbidities (n = 41) ≥ 18 years of age. Most studies were conducted in Europe (n = 44), Asia (n = 40), and North America (n = 36). Postherpetic neuralgia (PHN) was the most studied neurological complication. Variable relative PHN incidence was found in the general population (2.6-46.7%) or based on diagnosis: immunocompromised (3.9-33.8%), depression (0-50%), and human immunodeficiency virus (HIV) (6.1-40.2%). High incidence rates were observed in hematological malignancies (HM) and solid organ malignancies (132.5 and 93.7 per 1000 person-years, respectively). Ocular complications were frequently reported with herpes zoster ophthalmicus (HZO). The relative incidence (incidence rate) of HZO in the general population was reported as 1.4-15.9% (0.31-0.35 per 1000 person-years). High relative incidence was observed in HIV (up to 10.1%) and HM (3.2-11.3%). Disseminated HZ was the most frequently reported cutaneous complication. The relative incidence of disseminated HZ was 0.3-8.2% in the general population, 0-0.5% in the immunocompetent, and 0-20.6% in patients with comorbidities. High relative incidence was reported in HM and solid organ transplant (up to 19.3% and 14.8%, respectively). DISCUSSION: Most reported complications were neurological (n = 110), ocular (n = 48), and cutaneous (n = 38). Few studies stratified complications by age or gender (or both). Incidence appeared higher in select immunocompromised populations. Higher incidence was associated with older age in several studies; the general association with gender was unclear. CONCLUSIONS: Variable incidence of HZ complications was reported by population subgroup. Further research is required to quantitatively analyze incidence by age, gender, and location.

Public Health Impact of the Adjuvanted RSVPreF3 Vaccine for Respiratory Syncytial Virus Prevention Among Older Adults in the United States.

INTRODUCTION: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. METHODS: This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60 years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). RESULTS: In the base-case analysis, approximately 56.7 million adults aged ≥ 60 years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3 years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. CONCLUSIONS: These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60 years.

The respiratory syncytial virus prefusion F protein vaccine attenuates the severity of respiratory syncytial virus-associated disease in breakthrough infections in adults ≥60 years of age.

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022). Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models. Results: In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p = 0.1695). Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility.

Cost-effectiveness of the recombinant zoster vaccine (RZV) against herpes zoster: An updated critical review.

The objective of this study was to critically review the cost-effectiveness (CE) of the recombinant zoster vaccine (RZV) against herpes zoster (HZ). A literature review was conducted in PubMed, Embase, and Cochrane between January 1, 2017, and February 28, 2022, and on select public healthcare agency websites to identify and collect data from CE studies comparing RZV to zoster vaccine live (ZVL) or to no vaccination. Study characteristics, inputs, and outputs were collected. The overall CE of RZV was assessed. RZV vaccination against HZ is cost-effective in 15 out of 18 studies included in the present review. Varying incremental cost-effectiveness ratios (ICERs) observed may be associated with different assumptions on the duration of protection of RZV, as well as different combinations of structural and disease-related study (model) inputs driving the estimation of ICERs.

What is the context?• Herpes zoster, also known as shingles, may cause painful rashes and skin alterations.• Chronic pain, also referred to as post-herpetic neuralgia, may persist for months or even years after the initial rash.• The disease is caused by reactivation of the varicella zoster virus.• The recombinant zoster vaccine (RZV) and the zoster vaccine live (ZVL) are approved for the prevention of herpes zoster and post-herpetic neuralgia.• We reviewed published evidence from the past 5 years on RZV.What is new?• Out of 18 selected studies, RZV vaccination against herpes zoster and post-herpetic neuralgia is cost-effective in 15.• In the 15 studies establishing RZV cost-effectiveness, RZV is always cost-effective or frequently cost-saving in direct comparisons to ZVL, when applicable.• RZV was found cost-saving in several immune-compromised populations.What is the impact?• The overview of the currently available body of evidence related to cost-effectiveness of RZV may help informing decision makers about the value of vaccination against herpes zoster.

Healthy ageing: Herpes zoster infection and the role of zoster vaccination.

Populations are ageing worldwide, with considerable time lived in ill-health, putting upwards pressure on healthcare budgets. Healthy ageing is defined as maintaining functional ability, including the ability to: meet basic needs; learn, grow and make decisions; be mobile; build and maintain relationships; and contribute to society. The risk and impact of infectious diseases increase with age due to immunosenescence. Vaccination can help to prevent disease in older adults, promoting healthy ageing and active lives. Herpes zoster (HZ) occurs when the varicella zoster virus is reactivated due to declining immunity. HZ is common, with a lifetime risk of one-third, and increases in incidence with age. HZ is associated with severe and intense pain, substantially affecting the functional status of patients as well as their overall health-related quality of life. HZ and its complications may result in prolonged morbidity, including persistent pain (post-herpetic neuralgia, PHN), hearing impairment, vision loss and increased risk of stroke and myocardial infarction. HZ and PHN are difficult to treat, substantiating the benefits of prevention. Vaccines to prevent HZ include a recombinant zoster vaccine (RZV). RZV has shown efficacy against the HZ burden of disease and HZ burden of interference on activities of daily living of over 90% in immunocompetent adults aged ≥50 years. Vaccine efficacy against HZ was maintained at over 70% at 10 years post-vaccination. Adult vaccination, including against HZ, has the potential to reduce burden of disease, thus helping to maintain functioning and quality of life to support healthy ageing in older adults.

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

INTRODUCTION: Recombinant 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: Modestly 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.

Recombinant zoster vaccine in immunocompetent and immunocompromised adults: A review of clinical studies.

Herpes zoster (HZ) is a debilitating vaccine-preventable disease. Impairment of cell-mediated immunity, as observed with aging and immunosuppressive disorders and therapies, increases risk. Recombinant zoster vaccine (RZV) is efficacious against HZ in adults aged ≥50 years in different settings, and in immunocompromised adults aged ≥18 years who are at increased risk of developing HZ. RZV is the first and only HZ vaccine approved for use in immunocompromised adults globally, including in Europe and the US. RZV has a clinically acceptable safety profile and elicits robust immune responses in adults aged ≥50 years, and in immunocompromised adults aged ≥18 years who are at increased risk of HZ. Additionally, RZV is efficacious against HZ complications such as post-herpetic neuralgia and HZ-related pain. This review updates knowledge from a randomized controlled trial setting on the efficacy, safety, immunogenicity, and impact on quality of life of RZV.

What is the context?The varicella zoster virus, which causes chickenpox in childhood, can reactivate in adults and trigger a painful rash called herpes zoster (HZ) or shingles. Almost all adults are at risk of developing HZ as they age or develop risk factors for HZ. Two key studies published in 2015 and 2016 (ZOE-50 and ZOE-70) compared the recombinant zoster vaccine (RZV) with placebo and showed that RZV could effectively prevent HZ in adults aged ≥50 years and ≥70 years, respectively. Several clinical studies were carried out in subsequent years, assessing how effective and safe RZV is compared with a placebo/control in different populations. Based on these studies, RZV was approved for use in adults aged ≥50 years and those aged ≥18 years at increased risk of HZ (European Union) due to immunodeficiency or immunosuppression caused by known disease or therapy (United States).What is new?We reviewed clinical studies of RZV published between 1 January, 2015 and 31 October, 2022. The evidence shows that RZV is effective and does not cause safety concerns across the studied populations, including adults aged ≥50 years and immunocompromised adults aged ≥18 years who are at increased risk of HZ.What is the impact?The growing amount of knowledge on the efficacy, safety, immunogenicity, and impact on quality of life of RZV should assist in deciding to vaccinate and in ensuring that the individuals who could benefit the most from RZV have access to vaccination.

An Analysis of How Herpes Zoster Pain Affects Health-related Quality of Life of Placebo Patients From 3 Randomized Phase III Studies.

OBJECTIVES: Herpes zoster (HZ) is a painful condition caused by the reactivation of the varicella-zoster virus, negatively affecting the lives of patients. In this post hoc analysis, we describe the impact of HZ pain on the health-related quality of life (HRQoL) and activities of daily living (ADL) of immunocompetent individuals 50 years of age and older and in hematopoietic stem cell transplantation (HSCT) recipients age 18 years of age and older. MATERIALS AND METHODS: ZOE-50 (NCT01165177), ZOE-70 (NCT01165229), and ZOE-HSCT (NCT01610414) were phase III, randomized studies conducted in immunocompetent adults 50 years of age and older and 70 years of age and older and in HSCT recipients age 18 years of age and older, respectively. This analysis was performed on patients who experienced an HZ episode in the placebo groups. The impact of varying levels of HZ pain on HRQoL and ADL was analyzed using data from the Zoster Brief Pain Inventory (ZBPI) and the Short Form Health Survey 36 (SF-36) and EQ-5D questionnaires. RESULTS: A total of 520 immunocompetent and 172 HSCT individuals with HZ were included. SF-36 and EQ-5D domain scores showed a significant relationship between increased HZ pain and worsening HRQoL. For every increase of 1 in the ZBPI pain score, the estimated mean decrease (worsening) in score in the ZOE-50/70 and ZOE-HSCT, respectively, was 2.0 and 2.4 for SF-36 Role Physical; 2.1 and 1.8 for SF-36 Social Functioning; and 0.041 and 0.045 for EQ-5D utility. Sleep and General activities were the ADL components most affected. DISCUSSION: Moderate and severe HZ pain had a substantial negative impact on all aspects of HRQoL and ADL. This impact was independent of age and immunosuppression.

Public health impact of recombinant zoster vaccine for prevention of herpes zoster in US adults immunocompromised due to cancer.

Individuals who are immunocompromised (IC) due to therapy or underlying disease are at increased risk of herpes zoster (HZ). This study evaluates the public health impact of recombinant zoster vaccine (RZV) relative to no HZ vaccination for the prevention of HZ among adults aged ≥18 years diagnosed with selected cancers in the United States (US). A static Markov model was used to simulate three cohorts of individuals who are IC with cancer (time horizon of 30 years; one-year cycle length): hematopoietic stem cell transplant (HSCT) recipients, patients with breast cancer (BC; a solid tumor example), and patients with Hodgkin's lymphoma (HL; a hematological malignancy example). Cohort sizes reflect the estimated annual incidence of each condition in the US population (19,671 HSCT recipients, 279,100 patients with BC, and 8,480 patients with HL). Vaccination with RZV resulted in 2,297; 38,068; and 848 fewer HZ cases for HSCT recipients, patients with BC, and patients with HL, respectively (each versus no vaccine). Vaccination with RZV also resulted in 422; 3,184; and 93 fewer postherpetic neuralgia cases for HSCT, BC, and HL, respectively. Analyses estimated the quality-adjusted life years gained to be 109, 506, and 17 for HSCT, BC, and HL, respectively. To prevent one HZ case, the number needed to vaccinate was 9, 8, and 10, for HSCT, BC, and HL, respectively. These results suggest RZV vaccination may be an effective option to significantly reduce HZ disease burden among patients diagnosed with selected cancers in the US.

Shingles cases can be prevented by recombinant zoster vaccine (RZV). People who have a weakened immune system (immunocompromised) due to disease or therapy are more likely to develop shingles. For example, shingles occurs in nearly a quarter of patients receiving immunosuppressive treatment for blood cancers. To estimate the public health impact of vaccination against shingles in people who are immunocompromised due to cancer in the United States (US), we used a model to simulate groups with selected types of cancer. The results indicate vaccination with RZV can significantly reduce shingles cases and related complications among these groups in the US.

Adjuvanted recombinant zoster vaccine decreases herpes zoster-associated pain and the use of pain medication across 3 randomized, placebo-controlled trials.

ABSTRACT: Herpes zoster (HZ) and HZ-associated pain greatly affect patients' quality of life, particularly in older and immunocompromised adults, for whom comorbidities and polypharmacy are often reported. Three phase III, randomized, placebo-controlled clinical trials have reported the adjuvanted recombinant zoster vaccine (RZV) as highly efficacious in preventing HZ and reducing pain severity in healthy adults ≥50 years old (Zoster Efficacy Study [ZOE]-50 study, NCT01165177) and ≥70 years old (ZOE-70; NCT01165229) and in immunocompromised adults ≥18 years old undergoing autologous hematopoietic stem cell transplantation (ZOE-HSCT; NCT01610414). Here, we investigated efficacy of RZV in reducing (i) the duration of clinically significant pain (Zoster Brief Pain Inventory pain score ≥3) and (ii) HZ-associated pain medication use and duration of use in participants with confirmed HZ ("breakthrough cases") from the 3 studies. Recombinant zoster vaccine effectively reduced the duration of clinically significant HZ-associated pain during HZ episodes by 38.5% ( P -value: 0.010) in the ZOE-HSCT study. Although a similar trend was observed in the ZOE-50 and ZOE-70 studies, the results were not statistically significant because of the high vaccine efficacy (VE) against HZ resulting in rare breakthrough cases. VE in reducing pain medication use (39.6%; P -value: 0.008) and duration of medication use (49.3%, P -value: 0.040) was reported in the ZOE-70 study; corresponding positive VE estimates were observed in the ZOE-50 and ZOE-HSCT studies but were not statistically significant. Data reported here demonstrate efficacy of RZV in reducing HZ-associated pain duration and pain medication use in breakthrough cases, thereby improving quality of life of those with HZ.

Lifetime risk of herpes zoster in the population of Beijing, China.

Objectives: We aimed to estimate the current and future lifetime risks (LTR) of herpes zoster (HZ) and postherpetic neuralgia (PHN), as well as their respective number of annual incident cases in Beijing, China, if individuals were not vaccinated against HZ. Study design: Mathematical model built in Microsoft Excel, de novo. Methods: A hypothetical cohort of 1,000 people was simulated from age 0-100 or until death to generate LTRs of HZ/PHN in Beijing, China. LTR was defined as the risk of developing HZ/PHN at least once in the person's lifetime. The current number of annual incident HZ/PHN cases were also calculated by multiplying up-to-date population data and the annual age-specific incidence of HZ/PHN. For both LTR and annual incident cases, current estimates were projected into the year 2035 to investigate the impact of an aging population. Scenario and deterministic sensitivity analyses (DSA) were conducted to validate the model outcomes. Results: In Beijing, the current and future LTRs of HZ (PHN) were 32.4% (2.8%) and 34.8% (3.3%), respectively. The current and future annual incident cases of HZ (PHN) of individuals aged ≥50 years were 68,394 (7,801) cases among 7.04 million individuals and 88,676 (9,649) cases among 9.08 million individuals, respectively. The scenario analyses demonstrated that modelled results were likely to underestimate the LTR of HZ. Results were robust under the DSA. Conclusions: Given an aging population, HZ poses a significant, growing burden on individuals, the society, and healthcare system of China, highlighting the need for preventative measures such as vaccination.