209696 - A targeted safety study, EPI-ZOSTER-032 VS US DB, to evaluate the safety of Shingrix in adults ≥ 65 years of age in the United States.

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Targeted safety study (TSS) and a post-authorization safety study (PASS)

Study drug and medical condition

• Medicinal product name:
  SHINGRIX
• Study drug International non-proprietary name (INN) or common name:
  HERPES ZOSTER VACCINE (RECOMBINANT, ADJUVANTED)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BK03) zoster, purified antigen

  zoster, purified antigen
• Medical condition to be studied:
  Herpes zoster

Population studied

• Short description of the study population:
  The study population included patients aged 65 years or older who had received at least one dose of Shingrix, recombinant zoster vaccine (RZV) for the treatment of herpes zoster identified from CMS chronic conditions warehouse Medicare database from January 2017 to December 2021. ; Inclusion criteria:; US Medicare beneficiaries who meet the following criteria will be included in the study:; 1. Age 65 and older at the date of the RZV vaccination or preventive care visit for the RZV unvaccinated comparator; 2. Enrolled in Medicare due to age or ESRD as the original and current qualifying reason; 3. Continuously enrolled in Medicare Parts A, B, and D fee-for-service for at least 365 days preceding the date of RZV vaccination or preventive care visit for the RZV unvaccinated comparator. Continuous enrollment is determined by Medicare enrollment in the month of the RZV vaccination or preventative care visit and enrollment in at least 11 of the 12 preceding months.; ; Exclusion criteria:; Beneficiaries who satisfy the following criteria will be excluded:; 1. Continuously enrolled only in Medicare Part C in the baseline period, OR; 2. Enrolled in Medicare due to disability as the original qualifying reason for enrollment.
• Age groups:
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  723.000

Study design details

• Study design:
  Self-Controlled Risk Interval (SCRI) study design. A cohort design was implemented to assess the risk of new onset PMR, GCA and ION within 183 days following RZV vaccination compared to an RZV-unvaccinated cohort who had a preventive care visit.
• Main study objective:
  To assess whether Shingrix, or RZV, is associated with an increased risk of new-onset Guillain-Barré Syndrome (GBS), Gout, Polymyalgia Rheumatica (PMR), Giant Cell Arteritis (GCA), Ischemic Optic Neuropathy (ION) or Supraventricular Tachycardia (SVT) within specified time periods after vaccination in people ≥ 65 years of age beginning January 2018 in CMS Medicare.
• Setting:
  The source population includes US adults age 65 and older who are enrolled in Medicare any time from 2017 through 2021.
• Comparators:
  RZV unvaccinated comparators
• Outcomes:
  The risk of new onset GBS (within 42 days) and Gout (within 30 days) following RZV vaccination using a Self-controlled Risk Interval (SCRI) design and the risk of new onset PMR (within 183 days) and GCA (within 183 days) following RZV vaccination using a cohort design. The risk of new onset SVT within 30 days following RZV vaccination using a SCRI design and the risk of new onset ION within 183 days following RZV vaccination using a cohort design.
• Data analysis plan:
  The analysis plan will include descriptive measures to characterize exposed and unexposed individuals, conditional Poisson regression models for the SCRI, and Cox proportional hazards regression models for the cohort design outcomes For each outcome there is a primary analysis, secondary analysis and sensitivity analysis All the statistical analyses will be done in Statistical Analysis System 9.4. All the statistical tests will be two-sided at alpha level of 0.05. All 95% confidence intervals will be estimated as the point estimate +/- 1.96*standard error.
• Summary results:
  In the primary analysis of outcomes evaluated using the SCRI design, that did not distinguish between doses, the RR of new onset GBS was 3.15 (95% CI: 1.82, 5.68) and the AR was 6.59 per 1 000 000 vaccine doses (95% CI: 4.35, 7.96), the RR of new onset gout was 1.00 (95% CI: 0.90, 1.12, and the RR of new onset SVT was 0.94 (95% CI: 0.89, 0.99). The primary analysis of outcomes evaluated using a cohort design, that evaluated the risk ; after Dose 1 and Dose 2 separately, did not show a statistically significant risk of PMR from Day 1 to 120 following Dose 1 (HR=1.00; 95% CI: 0.92, 1.09). After Day 120, there was a statistically significant increased risk of PMR following Dose 1: HR=2.05 (95% CI: 1.71, 2.46). The results did not reveal a statistically significant increased risk of GCA from Day 1 to 150 following RZV Dose 1 (HR=1.10; 95% CI: 0.94, 1.28) or after Day 150 (HR=1.34; 95% CI: 0.89, 2.01). Results from the Dose 2 primary analysis did not show an increased risk of GCA. The primary analysis using an IPTW stabilized weighted Cox proportional hazards regression analysis did not reveal a statistically significant risk of ION following RZV Dose 1 (HR=0.97, 95% CI: 0.90, 1.05) but showed a statistically significant lower risk of ION following RZV Dose 2 (HR=0.85, 95% CI: 0.78, 0.93) relative to the RZV-unvaccinated comparators.