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Myron J. Levin - One of the best experts on this subject based on the ideXlab platform.
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post hoc analysis of reactogenicity trends between dose 1 and dose 2 of the adjuvanted recombinant Zoster Vaccine in two parallel randomized trials
Human Vaccines & Immunotherapeutics, 2020Co-Authors: Romulo Colindres, Myron J. Levin, Lidia Oostvogels, Caroline Hervé, Valentine Wascotte, Alain Brecx, Christopher J P Clarke, Joon Hyung Kim, Toufik Zahaf, Anne SchuindAbstract:In two large clinical trials (ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]), two doses of the adjuvanted recombinant Zoster Vaccine (RZV) demonstrated >90% efficacy against herpes Zoster in adults...
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understanding the immunology of shingrix a recombinant glycoprotein e adjuvanted herpes Zoster Vaccine
Current Opinion in Immunology, 2019Co-Authors: Thomas C. Heineman, Anthony L Cunningham, Myron J. LevinAbstract:Herpes Zoster is common in older and immune suppressed persons due to diminished VZV-specific cellular immunity. A recombinant herpes Zoster Vaccine (RZV) consisting of a single VZV glycoprotein and an adjuvant system stimulates robust and persistent VZV-specific antibody and CD4+ T cell responses in these high-risk populations. VZV-specific immune responses induced by RZV, including the generation of polyfunctional T cells, are driven by the synergistic actions of the components of the Vaccine adjuvant system. RZV provides unprecedented protection against herpes Zoster in older adults regardless of age at vaccination and is efficacious in immune suppressed populations. Adjuvanted subunit antigens may represent a general strategy for Vaccines in the elderly and other individuals typically considered immunologically resistant to vaccination.
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Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant Zoster Vaccine: a pooled post-hoc analysis of two parallel randomized trials
Human vaccines & immunotherapeutics, 2019Co-Authors: Lidia Oostvogels, Myron J. Levin, Alemnew F Dagnew, Toufik Zahaf, Thomas C. Heineman, Robert W. Johnson, Janet E. Mcelhaney, Peter Van Den Steen, Roman Chlibek, Javier Díez-domingoAbstract:In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant Zoster Vaccine (RZV) demonstrated >90% efficacy against herpes Zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT0116...
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Herpes Zoster and Herpes Zoster Vaccine Rates Among Adults Living With and Without HIV in the Veterans Aging Cohort Study.
Journal of acquired immune deficiency syndromes (1999), 2018Co-Authors: Kellie L. Hawkins, Myron J. Levin, Adriana Weinberg, Kirsha S. Gordon, Catherine Battaglia, Maria C. Rodriguez-barradas, Sheldon T. Brown, David Rimland, Amy C. Justice, Janet P. TateAbstract:BACKGROUND Despite historically high rates of herpes Zoster among people living with HIV (PLWH), comparative studies of herpes Zoster by HIV serostatus are lacking since the advent of combination antiretroviral therapy and availability of Zoster Vaccine. METHODS Annual rates (2002-2015) of first-episode herpes Zoster and Zoster vaccination were calculated for PLWH and uninfected adults in the Veterans Aging Cohort Study and stratified by HIV serostatus and age. Herpes Zoster was captured using ICD9 codes and Vaccine receipt with procedural codes and pharmacy data. RESULTS Of 45,177 PLWH and 103,040 uninfected veterans, rates of herpes Zoster decreased among PLWH (17.6-8.1/1000) over the study period but remained higher than uninfected adults (4.1/1000) at the end of study period. Rates were higher in PLWH with lower CD4 ( 500 cells/µL: 18.0 vs 6.8/1000) and unsuppressed vs suppressed HIV-1 RNA (21.8 vs 7.1/1000). Restricted to virologically suppressed participants with CD4 >350 cells per microliter, herpes Zoster rates were similar among PLWH aged younger than 60 years and aged 60 years and older in 2015 (6.6 vs 6.7/1000) but higher than all uninfected age groups. At study end, cumulative receipt of Zoster Vaccine for PLWH aged 60 years and older was less than half that of uninfected veterans: 98.7 vs 215.2/1000. CONCLUSIONS Herpes Zoster rates among PLWH have markedly decreased, but, even in cART-treated individuals, remain 50% higher than uninfected adults. Lower rates of Zoster Vaccine receipt combined with high rates of herpes Zoster support the need for a safe and effective Vaccine against herpes Zoster for PLWH, formal Zoster Vaccine guidelines for PLWH, and consideration for expanded use at younger ages.
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varicella Zoster virus dna in blood after administration of herpes Zoster Vaccine
The Journal of Infectious Diseases, 2018Co-Authors: Myron J. Levin, Nadine Rouphael, Aneesh K. Mehta, Guangyun Cai, Katherine S Lee, Jennifer Canniff, Mark J Mulligan, Adriana WeinbergAbstract:We studied the relationship between varicella-Zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated Zoster Vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 Vaccinees. PCR was positive in 56% (9 direct, 28 nested) on day 1 and in 16% (1 direct, 10 nested) on day 14. Teff progressively increased in direct-PCR-positive Vaccinees up to day 30, but Tmem did not. Conversely, Tmem, but not Teff, increased in direct-PCR-negative Vaccinees on day 7. The kinetics of these immune responses and VZV DNAemia suggested that direct-PCR sample positive represented viremia.
Adriana Weinberg - One of the best experts on this subject based on the ideXlab platform.
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Herpes Zoster and Herpes Zoster Vaccine Rates Among Adults Living With and Without HIV in the Veterans Aging Cohort Study.
Journal of acquired immune deficiency syndromes (1999), 2018Co-Authors: Kellie L. Hawkins, Myron J. Levin, Adriana Weinberg, Kirsha S. Gordon, Catherine Battaglia, Maria C. Rodriguez-barradas, Sheldon T. Brown, David Rimland, Amy C. Justice, Janet P. TateAbstract:BACKGROUND Despite historically high rates of herpes Zoster among people living with HIV (PLWH), comparative studies of herpes Zoster by HIV serostatus are lacking since the advent of combination antiretroviral therapy and availability of Zoster Vaccine. METHODS Annual rates (2002-2015) of first-episode herpes Zoster and Zoster vaccination were calculated for PLWH and uninfected adults in the Veterans Aging Cohort Study and stratified by HIV serostatus and age. Herpes Zoster was captured using ICD9 codes and Vaccine receipt with procedural codes and pharmacy data. RESULTS Of 45,177 PLWH and 103,040 uninfected veterans, rates of herpes Zoster decreased among PLWH (17.6-8.1/1000) over the study period but remained higher than uninfected adults (4.1/1000) at the end of study period. Rates were higher in PLWH with lower CD4 ( 500 cells/µL: 18.0 vs 6.8/1000) and unsuppressed vs suppressed HIV-1 RNA (21.8 vs 7.1/1000). Restricted to virologically suppressed participants with CD4 >350 cells per microliter, herpes Zoster rates were similar among PLWH aged younger than 60 years and aged 60 years and older in 2015 (6.6 vs 6.7/1000) but higher than all uninfected age groups. At study end, cumulative receipt of Zoster Vaccine for PLWH aged 60 years and older was less than half that of uninfected veterans: 98.7 vs 215.2/1000. CONCLUSIONS Herpes Zoster rates among PLWH have markedly decreased, but, even in cART-treated individuals, remain 50% higher than uninfected adults. Lower rates of Zoster Vaccine receipt combined with high rates of herpes Zoster support the need for a safe and effective Vaccine against herpes Zoster for PLWH, formal Zoster Vaccine guidelines for PLWH, and consideration for expanded use at younger ages.
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varicella Zoster virus dna in blood after administration of herpes Zoster Vaccine
The Journal of Infectious Diseases, 2018Co-Authors: Myron J. Levin, Nadine Rouphael, Aneesh K. Mehta, Guangyun Cai, Katherine S Lee, Jennifer Canniff, Mark J Mulligan, Adriana WeinbergAbstract:We studied the relationship between varicella-Zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated Zoster Vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 Vaccinees. PCR was positive in 56% (9 direct, 28 nested) on day 1 and in 16% (1 direct, 10 nested) on day 14. Teff progressively increased in direct-PCR-positive Vaccinees up to day 30, but Tmem did not. Conversely, Tmem, but not Teff, increased in direct-PCR-negative Vaccinees on day 7. The kinetics of these immune responses and VZV DNAemia suggested that direct-PCR sample positive represented viremia.
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Zoster Vaccine in young and elderly
2018Co-Authors: Nadine Rouphael, Myron J. Levin, Aneesh K. Mehta, Adriana WeinbergAbstract:Double center, open label study in which adult healthy volunteers will be vaccinated with Zoster Vaccine.
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varicella Zoster virus specific cellular immune responses to the live attenuated Zoster Vaccine in young and older adults
Journal of Immunology, 2017Co-Authors: Adriana Weinberg, Nadine Rouphael, Aneesh K. Mehta, Jennifer Canniff, Mark J Mulligan, Jennifer A Whitaker, Myron J. LevinAbstract:The incidence and severity of herpes Zoster (HZ) increases with age. The live attenuated Zoster Vaccine generates immune responses similar to HZ. We compared the immune responses to Zoster Vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-Zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4+ and CD8+ T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8+CD57+ senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4+CD69+CD57+PD1+ and CD8+CD69+CD57+PD1+ T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8+ effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4+ and CD8+ proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ.
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varicella Zoster virus specific immune responses to a herpes Zoster Vaccine in elderly recipients with major depression and the impact of antidepressant medications
Clinical Infectious Diseases, 2013Co-Authors: Michael R Irwin, Myron J. Levin, Michael J Caulfield, Harold A Stanley, Mark L Laudenslager, Richard G Olmstead, Anne Lucko, Nancy Lang, Carmen Carrillo, Adriana WeinbergAbstract:Background. The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella Zoster virus (VZV) Vaccine (Zoster Vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes Zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults ≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative Zoster Vaccine efficacy study. Methods. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with Zoster Vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Results. Depressed subjects who were not treated with antidepressant medications had lower levels of VZVCMI following administration of Zoster Vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P< .005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Conclusions. Depressed patients have diminished VZV-CMI responses to Zoster Vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of Zoster Vaccine.
Kenneth E. Schmader - One of the best experts on this subject based on the ideXlab platform.
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Long-term Persistence of Zoster Vaccine Efficacy
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014Co-Authors: Vicki A. Morrison, Gary R. Johnson, Kenneth E. Schmader, Myron J. Levin, Jane H. Zhang, David Looney, Robert F. Betts, Larry D. Gelb, John C. Guatelli, Ruth HarbeckeAbstract:Background. The Shingles Prevention Study (SPS) demonstrated Zoster Vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of Vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess Vaccine efficacy in SPS Vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered Zoster Vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS Vaccine recipients. Compared to SPS, estimated Vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes Zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas Vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of Vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant Vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant Vaccine efficacy for incidence of HZ persisted only through year 8.
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Editorial Commentary: Zoster Vaccine in Immunocompromised Patients: Time to Reconsider Current Recommendations
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014Co-Authors: Michael N. Oxman, Kenneth E. SchmaderAbstract:Reduced cell-mediated immunity (CMI) to varicella Zoster virus (VZV) is associated with an increase in the risk and severity of herpes Zoster (HZ) and its debilitating complications, including postherpetic neuralgia (PHN). This is true whether the reduction in VZV CMI is due to the age-related decline in CMI observed in normal older adults, or to immunosuppression caused by certain diseases or their treatments. Zoster Vaccines containing the Oka strain of live attenuated VZV have proven to be safe and effective inolderadults, but currentrecommendations preclude their use in immunocompromised persons. In this issue of Clinical Infectious Diseases, Tseng et al [1] report that Zoster Vaccine, administered to adults ≥60 years of age, continued to protect against HZ when recipients subsequently underwent cancer chemotherapy. These findings underline the importance of administering Zoster Vaccine to immunocompetent older adults as currently recommended [2], and doing so as early as possible. In addition, the results of these and similar studies suggest that it may be time to review the current policy of excluding all immunocompromised persons from receiving Zoster Vaccine. The study by Tseng et al [1] was conducted among members of Kaiser Permanente Southern California (KPSC), an integrated healthcare system that pro
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safety of Zoster Vaccine in elderly adults following documented herpes Zoster
The Journal of Infectious Diseases, 2013Co-Authors: Vicki A. Morrison, Kenneth E. Schmader, Myron J. Levin, Robert F. Betts, John C. Guatelli, Michael N. Oxman, Constance T. Pachucki, Susan Keay, Larry Gelb, Barbara MenziesAbstract:Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational Zoster Vaccine without charge. This provided an opportunity to determine the relative safety of Zoster Vaccine in older adults following documented herpes Zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive Zoster Vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving Zoster Vaccine. The SPS placebo recipients who received Zoster Vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of Zoster Vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. Conclusions. These results demonstrate that the general safety of Zoster Vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer Zoster Vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ.
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safety of Zoster Vaccine in elderly adults following documented herpes Zoster
The Journal of Infectious Diseases, 2013Co-Authors: Vicki A. Morrison, Kenneth E. Schmader, Myron J. Levin, Robert F. Betts, John C. Guatelli, Michael N. Oxman, Constance T. Pachucki, Susan Keay, Larry Gelb, Barbara MenziesAbstract:A large randomized double-blind placebo-controlled clinical trial, Department of Veterans Affairs Cooperative Study Program (VA CSP) Number 403: the Shingles Prevention Study (SPS), conducted in 38 546 ambulatory immunocompetent adults ≥60 years of age, demonstrated that a live attenuated Oka/Merck varicella Zoster virus (VZV) Vaccine (hereafter, “Zoster Vaccine”) reduced the burden of illness due to herpes Zoster (HZ)–related pain and/or discomfort by 61%, the incidence of postherpetic neuralgia by 67%, and the incidence of HZ by 51% [1]. Vaccine efficacy is thought to result from a Vaccine-induced increase in VZV-specific cell-mediated immunity [2–4]. Zoster Vaccine (Zostavax, Merck Sharp & Dohme) was licensed by the US Food and Drug Administration in 2006 for the prevention of HZ in immunocompetent adults ≥60 years of age, and is recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices for routine administration to eligible adults ≥60 years of age, regardless of a prior history of HZ [5, 6]. The rationale for administration of Zoster Vaccine irrespective of prior HZ includes the (1) questionable reliability of a self-reported history of HZ, (2) assumption that prior HZ will not increase the incidence or severity of adverse events associated with administration of Zoster Vaccine, and (3) lack of knowledge regarding the level and duration of protection induced by an episode of HZ. Data from the SPS indicate that increased levels of VZV-specific cell-mediated immunity induced by Zoster Vaccine or HZ often decline significantly to near baseline levels within 3 years after vaccination or HZ [3, 4]. Because subjects with prior HZ were excluded from the SPS, there is little direct evidence of the safety of Zoster Vaccine in subjects with prior HZ. A small study comparing Zoster Vaccine to placebo in 101 adults ≥50 years of age, all with a history of HZ ≥5 years prior to vaccination, indicated that the Vaccine was well tolerated and boosted titers of VZV antibody [7]. Beginning in 2005, SPS participants who had received placebo and could be contacted were offered Zoster Vaccine without charge, in accordance with the SPS protocol [1]. Because 420 of the 13 681 placebo recipients who received Zoster Vaccine had experienced an episode of documented HZ during the SPS, we compared the safety of Zoster Vaccine in these 420 subjects with documented HZ to the safety of Zoster Vaccine in the 13 261 SPS placebo recipients who had never experienced HZ.
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Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster
The Journal of infectious diseases, 2013Co-Authors: Vicki A. Morrison, Kenneth E. Schmader, Myron J. Levin, Robert F. Betts, Larry D. Gelb, John C. Guatelli, Michael N. Oxman, Constance T. Pachucki, Susan Keay, Barbara MenziesAbstract:Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational Zoster Vaccine without charge. This provided an opportunity to determine the relative safety of Zoster Vaccine in older adults following documented herpes Zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive Zoster Vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving Zoster Vaccine. The SPS placebo recipients who received Zoster Vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of Zoster Vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was
Hung Fu Tseng - One of the best experts on this subject based on the ideXlab platform.
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patient report of herpes Zoster pain incremental benefits of Zoster Vaccine live
Vaccine, 2019Co-Authors: Katia Bruxvoort, Anna S Liang, Rafael Harpaz, Lina S Sy, Scott D Schmid, Harmindar S. Takhar, Philip Larussa, Lei Qian, Hung Fu TsengAbstract:INTRODUCTION: Pain 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. METHODS: ZVL 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. RESULTS: We 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. CONCLUSION: We 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.
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Use of Real-world Evidence to Evaluate the Effectiveness of Herpes Zoster Vaccine.
The Journal of infectious diseases, 2018Co-Authors: Hung Fu TsengAbstract:This article reviews the use of real-world evidence (RWE) from observational studies to evaluate herpes Zoster Vaccine effectiveness and complement clinical trial data that have known limitations. The use of RWE with appropriate study designs and cautious interpretation can be informative in decision-making. Understanding the advantages and limitations of studies yielding RWE can facilitate the critical evaluation of findings from different studies. This is a timely issue, as regulatory agencies are considering how RWE can contribute to the assessment of effectiveness in regulatory decision-making.
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Real-World Evidence for Regulatory Decisions: Concomitant Administration of Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.
American journal of epidemiology, 2018Co-Authors: Katia Bruxvoort, Yi Luo, Hung Fu TsengAbstract:The US Food and Drug Administration is charged with expanding the use of real-world evidence for regulatory decisions. As a test case for real-world evidence to support regulatory decisions, we present the scenario of concomitant vaccination with Zoster Vaccine live (ZVL) and 23-valent pneumococcal polysaccharide Vaccine (PPSV23). The prescribing information states that these Vaccines should not be given concurrently, based on a small trial using varicella Zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL protects against herpes Zoster via cell-mediated immunity. We conducted an observational cohort study involving more than 35,000 members of Kaiser Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23 prior to ZVL. Occurrence of herpes Zoster was assessed through electronic health records from January 1, 2007, to June 30, 2016. The adjusted hazard ratio comparing incidence rates of herpes Zoster in the concomitant vaccination cohort and the prior vaccination cohort was 1.04 (95% confidence interval: 0.92, 1.16). This real-world evidence study provides direct evidence for a lack of Vaccine interference, relying on herpes Zoster occurrence rather than an intermediate marker of immunity. Real-world evidence is essential for regulators and policy makers in addressing evidentiary gaps regarding safety, effectiveness, compliance, and Vaccine interactions for the new recombinant Zoster Vaccine.
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Trends and disparity in Zoster Vaccine uptake in a managed care population.
Vaccine, 2013Co-Authors: Rulin C. Hechter, Ning Smith, Steven J. Jacobsen, Sara Y. Tartof, Hung Fu TsengAbstract:Abstract Objectives Zoster Vaccine is recommended for prevention of herpes Zoster among adults aged 60 years and older. We examined the Zoster vaccination rates during 2007–2011 and assessed association with age, sex, race/ethnicity, neighborhood income and education attainment in eligible adults at Kaiser Permanente Southern California, a managed care organization in the US. Methods We calculated annual Zoster vaccination rate among members ≥60 years without documented contraindications. Multivariable logistic regression was performed to examine factors associated with Zoster Vaccine uptake in an open cohort of 819,466 adults. Results The Zoster vaccination rates increased annually in all groups and the overall rate reached 21.7% in 2011 ( P -trend 75% vs. Conclusion The Zoster Vaccine coverage is higher in this insured population than previously reported in the US general population, but it remains low. Significant racial/ethnic disparity was observed and worsened even among individuals with relatively equal access to Zoster vaccination.
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Safety of Zoster Vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study.
Journal of internal medicine, 2011Co-Authors: Hung Fu Tseng, Amy Liu, S. M. Marcy, Bruce Fireman, Eric Weintraub, James Baggs, Sheila Weinmann, Roger Baxter, James D. NordinAbstract:Abstract. Tseng HF, Liu A, Sy L, Marcy SM, Fireman B, Weintraub E, Baggs J, Weinmann S, Baxter R, Nordin J, Daley MF, Jackson L, Jacobsen SJ, for the Vaccine Safety Datalink (VSD) Team (Kaiser Permanente, Pasadena, CA; Kaiser Permanente, Oakland, CA; Centers for Disease Control and Prevention, Atlanta, GA; Kaiser Permanente, Portland, OR; HealthPartners Research Foundation, Minneapolis, MN; Kaiser Permanente, Denver, CO; and Group Health Cooperative of Puget Sound, Seattle, WA; USA). Safety of Zoster Vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study. J Intern Med 2012; 271: 510–520. Objectives. The aim of this study was to examine a large cohort of adults who received the Zoster Vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention. Design. Two self-comparison approaches, including a case-centred approach and a self-controlled case series (SCCS) analysis were used. Setting. Eight managed-care organizations participating in the Vaccine Safety Datalink project in the United States. Subjects. A total of 193 083 adults aged 50 and older receiving a Zoster Vaccine from 1 January 2007 to 31 December 2008 were included. Main outcome measures. Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD-9) codes in automated health plan datasets. Results. The risk of allergic reaction was significantly increased within 1–7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87–2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85–2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay-Hunt syndrome and Bell’s palsy. Conclusions. The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the Zoster Vaccine is generally safe and well-tolerated with a small increased risk of allergic reactions in 1–7 days after vaccination.
Gary R. Johnson - One of the best experts on this subject based on the ideXlab platform.
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Long-term Persistence of Zoster Vaccine Efficacy
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014Co-Authors: Vicki A. Morrison, Gary R. Johnson, Kenneth E. Schmader, Myron J. Levin, Jane H. Zhang, David Looney, Robert F. Betts, Larry D. Gelb, John C. Guatelli, Ruth HarbeckeAbstract:Background. The Shingles Prevention Study (SPS) demonstrated Zoster Vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of Vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess Vaccine efficacy in SPS Vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered Zoster Vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS Vaccine recipients. Compared to SPS, estimated Vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes Zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas Vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of Vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant Vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant Vaccine efficacy for incidence of HZ persisted only through year 8.
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persistence of the efficacy of Zoster Vaccine in the shingles prevention study and the short term persistence substudy
Clinical Infectious Diseases, 2012Co-Authors: Kenneth E. Schmader, Vicki A. Morrison, Gary R. Johnson, Myron J. Levin, Jane H. Zhang, Robert F. Betts, John C. Guatelli, Michael N. Oxman, Lawrence D. Gelb, Ruth HarbeckeAbstract:Herpes Zoster (HZ) results from the reactivation, multiplication, and spread of varicella-Zoster virus (VZV) that remains latent in sensory neurons following earlier primary VZV infection (ie, varicella or chickenpox) [1]. Department of Veterans Affairs (VA) Cooperative Study 403: The Shingles Prevention Study was a randomized, double-blind, placebo-controlled efficacy trial of live attenuated Oka/Merck HZ Vaccine (Zoster Vaccine) in 38 546 adults ≥60 years of age. The Shingles Prevention Study demonstrated that Zoster Vaccine reduced the HZ burden of illness by 61.1% (95% confidence interval [CI], 51.1–69.1), the incidence of postherpetic neuralgia (PHN) by 66.5% (95% CI, 47.5–79.2), and the incidence of HZ by 51.3% (95% CI, 44.2–57.6) through 4 years of postvaccination follow-up [2–4]. After the completion of the Shingles Prevention Study, a cohort of subjects was re-enrolled into a short-term persistence substudy. The Short-Term Persistence Substudy extended the follow-up of this cohort of subjects to collect data on the persistence of Zoster Vaccine efficacy for the 3 end points described above during the interval between the closeout of VA Cooperative Study 403 and the completion of the final data analysis. The Short-Term Persistence Substudy also provided a cohort of the original Shingles Prevention Study Vaccine recipients who could subsequently be enrolled in a long-term persistence substudy to further assess the persistence of Vaccine efficacy. In addition, data on the persistence of Vaccine efficacy for each year after vaccination in the Shingles Prevention Study have not been published. Therefore, the objectives of this article are to assess the persistence of Vaccine efficacy for the 3 study end points in the Short-Term Persistence Substudy population, the Shingles Prevention Study population, and the combined Shingles Prevention Study and Short-Term Persistence Substudy populations and to assess the persistence of Vaccine efficacy for the 3 study end points for each year through year 7 after subjects received Zoster Vaccine or placebo in the Shingles Prevention Study.
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Effect of a Zoster Vaccine on Herpes Zoster–Related Interference with Functional Status and Health‐Related Quality‐of‐Life Measures in Older Adults
Journal of the American Geriatrics Society, 2010Co-Authors: Kenneth E. Schmader, Gary R. Johnson, Myron J. Levin, Jane H. Zhang, Ivan S. F. Chan, Patricia Saddier, Maria M. Ciarleglio, William Wang, Shing‐shing Yeh, Ruth HarbeckeAbstract:Objective To determine the efficacy of a Zoster Vaccine on herpes Zoster related interference with activities of daily living (ADL) and health-related quality of life (HRQL).
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effect of a Zoster Vaccine on herpes Zoster related interference with functional status and health related quality of life measures in older adults
Journal of the American Geriatrics Society, 2010Co-Authors: Kenneth E. Schmader, Gary R. Johnson, Myron J. Levin, Jane H. Zhang, Ivan S. F. Chan, Patricia Saddier, Maria M. Ciarleglio, William Wang, Shingshing Yeh, Ruth HarbeckeAbstract:Objective To determine the efficacy of a Zoster Vaccine on herpes Zoster related interference with activities of daily living (ADL) and health-related quality of life (HRQL).
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Safety of Herpes Zoster Vaccine in the Shingles Prevention Study
Annals of Internal Medicine, 2010Co-Authors: Michael S. Simberkoff, Gary R. Johnson, Kenneth E. Schmader, Myron J. Levin, Michael N. Oxman, Robert D. Arbeit, Kathy D. Boardman, Heather M. Williams, Lawrence D. Gelb, Susan KeayAbstract:This secondary analysis from the Shingles Prevention Study focuses on the safety of the herpes Zoster Vaccine in immunocompetent adults older than 60 years. More Vaccine recipients than placebo rec...
