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Review
. 2021 Jul;44(7):811-823.
doi: 10.1007/s40264-021-01076-w. Epub 2021 Jun 11.

Safety Profile of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Populations: An Overview of Six Trials

Marta López-Fauqued  1 , Maribel Co-van der Mee  1 , Adriana Bastidas  1   2 , Pierre Beukelaers  1 , Alemnew F Dagnew  3   4 , Juan Jose Fernandez Garcia  5 , Anne Schuind  3   6 , Fernanda Tavares-da-Silva  7
Affiliations
Review

Safety Profile of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Populations: An Overview of Six Trials

Marta López-Fauqued et al. Drug Saf. 2021 Jul.

Abstract

Introduction: The adjuvanted recombinant zoster vaccine (RZV) has demonstrated high efficacy against herpes zoster in older adults and immunocompromised populations. We present comprehensive safety data from six clinical trials in immunocompromised populations (autologous hematopoietic stem cell transplant and renal transplant recipients, patients with hematologic malignancies, patients with solid tumors, and human immunodeficiency virus-infected adults) who are at an increased risk of herpes zoster.

Methods: In all trials, immunocompromised adults ≥ 18 years of age were administered RZV or placebo. Safety was evaluated in the total vaccinated cohort. Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs, fatal serious AEs, and potential immune-mediated diseases were collected from dose 1 until 12 months post-last dose or study end. Data were pooled for solicited AEs; unsolicited AEs, (fatal) serious AEs, and potential immune-mediated diseases were analyzed for each individual trial. All AEs were analyzed for sub-strata of adults 18-49 years of age and ≥ 50 years of age.

Results: In total, 1587 (RZV) and 1529 (placebo) adults were included in the pooled total vaccinated cohort. Solicited AEs were more common after RZV than placebo, were generally more common in the younger age stratum, and were mostly mild to moderate and resolved within 3 days (median duration). Unsolicited AEs and serious AEs were in line with underlying diseases and therapies. Across studies, the percentage of adults reporting one or more unsolicited AE was comparable between RZV and placebo, irrespective of age stratum. The percentage of adults reporting one or more serious AE, fatal serious AE, or potential immune-mediated diseases was generally similar for RZV and placebo, irrespective of age stratum. Overall, no safety concerns were identified.

Conclusions: Recombinant zoster vaccine has a clinically acceptable safety profile. With the previously published vaccine efficacy and immunogenicity results, these data support a favorable benefit-risk profile of RZV vaccination in immunocompromised populations who are at an increased risk of herpes zoster.

Plain language summary

Varicella zoster virus leads to chickenpox after primary infection and herpes zoster upon reactivation of the latent virus. Older adults and immunocompromised people, whose immune system is impaired because of the age-related decline in immunity and their underlying disease and/or treatment, respectively, are at an increased risk of herpes zoster and its complications. Recombinant zoster vaccine has been approved to prevent herpes zoster and its complications in adults aged ≥ 50 years in over 30 countries. In Europe, the vaccine has recently received approval to expand its use in adults aged 18 years or older who are at an increased risk of herpes zoster. We present an overview of the safety data from six clinical trials in immunocompromised patients vaccinated with recombinant zoster vaccine. We found that solicited adverse events were more common after the vaccine than placebo but that these were mild to moderate in intensity. Furthermore, the frequency of unsolicited adverse events was similar between the vaccine and placebo, and most of the reported adverse events and severe adverse events (e.g., infections or tumors) could be attributed to the pre-existent diseases and/or therapies. As such, no safety concern was identified following the review of the available clinical data. This overview, together with the published efficacy data in the prevention of herpes zoster and the vaccine immunogenicity, provides useful medical information and supports the use of the recombinant zoster vaccine in an immunocompromised population at an increased risk of herpes zoster.

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Conflict of interest statement

Maribel Co-van der Mee, Pierre Beukelaers, Juan Jose Fernandez Garcia, and Fernanda Tavares-da-Silva are employed by the GSK group of companies. Marta López-Fauqued, Juan Jose Fernandez Garcia, Adriana Bastidas, Alemnew F. Dagnew, and Anne Schuind were employees of the GSK group of companies during the design, initiation, conduct of the study and/or interpretation of the data. During the conduct of the study, Pierre Beukelaers, Juan Jose Fernandez Garcia, and Fernanda Tavares-da-Silva report personal fees from the GSK group of companies. Adriana Bastidas, Pierre Beukelaers, Alemnew F. Dagnew, Anne Schuind, and Fernanda Tavares-da-Silva hold shares in the GSK group of companies.

Figures

Fig. 1
Fig. 1
Unsolicited adverse events (AEs). auto-HSCT(I/II) autologous hematopoietic stem cell transplant recipients (phase I/II), auto-HSCT(III) autologous hematopoietic stem cell transplant recipients (phase III), HIV human immunodeficiency virus-infected adults, HM hematologic malignancies patients, RT renal transplant recipients, RZV adjuvanted recombinant zoster vaccine, ST solid tumors patients
Fig. 2
Fig. 2
Unsolicited adverse events (AEs) by age. a Adjuvanted recombinant zoster vaccine (RZV) and placebo in autologous hematopoietic cell transplant recipients [phase III] (Bastidas et al. [42]); b RZV and placebo in renal transplant recipients (Vink et al. [45]); c RZV and placebo in patients with hematologic malignancies (Dagnew et al. [43]); and d RZV and placebo in patients with solid organ tumors (Vink et al. [46]). Note: Figure panels present the percentage of RZV recipients reporting at least one unsolicited adverse event categorized under that Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Only the five SOCs with the greatest percentage of RZV recipients reporting any event are presented here. Because of the comparatively small sample sizes in the RZV groups in the studies with autologous hematopoietic cell transplant recipients (phase I/II) and human immunodeficiency virus-infected adults, we were not able to generate meaningful data for age strata in these studies
Fig. 3
Fig. 3
Serious adverse events (SAEs). auto-HSCT(I/II) autologous hematopoietic stem cell transplant recipients (phase I/II), auto-HSCT(III) autologous hematopoietic stem cell transplant recipients (phase III), HM hematologic malignancies patients, HIV human immunodeficiency virus-infected adults, RT, renal transplant recipients, RZV adjuvanted recombinant zoster vaccine, ST solid tumors patients
Fig. 4
Fig. 4
Serious adverse events (SAEs) by age. a Adjuvanted recombinant zoster vaccine RZV and placebo in autologous hematopoietic cell transplant recipients [phase III] (Bastidas et al. [42]); b RZV and placebo in renal transplant recipients (Vink et al. [45]); c RZV and placebo in patients with hematologic malignancies (Dagnew et al. [43]); and d RZV and placebo in patients with solid organ tumors (Vink et al. [46]). Figure panels present the percentage of RZV recipients reporting at least one unsolicited adverse event categorized under that Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Only the five SOCs with the greatest percentage of RZV participants reporting any event are presented here. Because of the comparatively small sample sizes in the RZV groups in the studies with autologous hematopoietic stem cell transplant recipients (phase I/II) and human immunodeficiency virus-infected adults, we were not able to generate meaningful data for age strata in these studies
Fig. 5
Fig. 5
Fatal serious adverse events (SAEs). auto-HSCT(I/II) autologous hematopoietic stem cell transplant recipients (phase I/II), auto-HSCT(III) autologous hematopoietic stem cell transplant recipients (phase III), HM hematologic malignancies patients, HIV human immunodeficiency virus-infected adults, RT renal transplant recipients, RZV adjuvanted recombinant zoster vaccine, ST solid tumors patients. The auto-HSCT(I/II) study includes data for both groups receiving two and three doses of RZV, respectively
Fig. 6
Fig. 6
Fatal serious adverse events (SAEs) by age. a Adjuvanted recombinant zoster vaccine (RZV) and placebo in autologous hematopoietic cell transplant recipients [phase III] (Bastidas et al. [42]); b RZV and placebo in renal transplant recipients (Vink et al. [45]); c RZV and placebo in patients with hematologic malignancies (Dagnew et al. [43]); and d RZV and placebo in patients with solid organ tumors (Vink et al. [46]). Figure panels present the percentage of RZV recipients reporting at least one unsolicited adverse event categorized under that Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Only the five SOCs with the greatest percentage of RZV participants reporting any event are presented here. Because of the comparatively small sample sizes in the RZV groups in the studies with autologous hematopoietic cell transplant recipients (phase I/II) and human immunodeficiency virus-infected adults, we were not able to generate meaningful data for age strata in these studies
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References

    1. Cohen JI. Clinical practice: herpes zoster. N Engl J Med. 2013;369(3):255–263. doi: 10.1056/NEJMcp1302674. - DOI - PMC - PubMed
    1. Kawai K, Gebremeskel BG, Acosta CJ. Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open. 2014;4(6):e004833. doi: 10.1136/bmjopen-2014-004833. - DOI - PMC - PubMed
    1. Tseng HF, Bruxvoort K, Ackerson B, Luo Y, Tanenbaum H, Tian Y, et al. The epidemiology of herpes zoster in immunocompetent, unvaccinated adults ≥ 50 years old: incidence, complications, hospitalization, mortality, and recurrence. J Infect Dis. 2020;222:798–806. doi: 10.1093/infdis/jiz652. - DOI - PMC - PubMed
    1. Gershon AA, Gershon MD, Breuer J, Levin MJ, Oaklander AL, Griffiths PD. Advances in the understanding of the pathogenesis and epidemiology of herpes zoster. J Clin Virol. 2010;48(Suppl. 1):S2–7. doi: 10.1016/S1386-6532(10)70002-0. - DOI - PMC - PubMed
    1. Weinberg A, Zhang JH, Oxman MN, Johnson GR, Hayward AR, Caulfield MJ, et al. Varicella-zoster virus-specific immune responses to herpes zoster in elderly participants in a trial of a clinically effective zoster vaccine. J Infect Dis. 2009;200(7):1068–1077. doi: 10.1086/605611. - DOI - PMC - PubMed

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