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Original Investigation
November 1, 2021

Risk of Guillain-Barré Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries

Author Affiliations
  • 1Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
  • 2Acumen, LLC
  • 3Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 4Department of Economics, Stanford University, Stanford, California
  • 5Centers for Medicare & Medicaid Services, Baltimore, Maryland
JAMA Intern Med. 2021;181(12):1623-1630. doi:10.1001/jamainternmed.2021.6227
Key Points

Question  Is there an increased risk of developing Guillain-Barré Syndrome (GBS) following vaccination with the recombinant zoster vaccine (RZV)?

Findings  In an observational study of Medicare beneficiaries, a medical record–based, self-controlled analysis of GBS cases after RZV vaccination identified a rate ratio of 2.84 between the risk and control windows, resulting in an attributable risk of 3 cases per million RZV (Shingrix) doses.

Meaning  These findings suggest that there is an increased risk of developing GBS following vaccination with RZV.

Abstract

Importance  Guillain-Barré syndrome can be reported after vaccination. This study assesses the risk of Guillain-Barré syndrome after administration of recombinant zoster vaccine (RZV or Shingrix), which is administered in 2 doses 2 to 6 months apart.

Objective  Use Medicare claims data to evaluate risk of developing Guillain-Barré syndrome following vaccination with zoster vaccine.

Design, Setting, and Participants  This case series cohort study included 849 397 RZV-vaccinated and 1 817 099 zoster vaccine live (ZVL or Zostavax)-vaccinated beneficiaries aged 65 years or older. Self-controlled analyses included events identified from 2 113 758 eligible RZV-vaccinated beneficiaries 65 years or older. We compared the relative risk of Guillain-Barré syndrome after RZV vs ZVL, followed by claims-based and medical record-based self-controlled case series analyses to assess risk of Guillain-Barré syndrome during a postvaccination risk window (days 1-42) compared with a control window (days 43-183). In self-controlled analyses, RZV vaccinees were observed from October 1, 2017, to February 29, 2020. Patients were identified in the inpatient, outpatient procedural (including emergency department), and office settings using Medicare administrative data.

Exposures  Vaccination with RZV or ZVL vaccines.

Main Outcomes and Measures  Guillain-Barré syndrome was identified in Medicare administrative claims data, and cases were assessed through medical record review using the Brighton Collaboration case definition.

Results  Amongst those who received RZV vaccinees, the mean age was 74.8 years at first dose, and 58% were women, whereas among those who received the ZVL vaccine, the mean age was 74.3 years, and 60% were women. In the cohort analysis we detected an increase in risk of Guillain-Barré syndrome among RZV vaccinees compared with ZVL vaccinees (rate ratio [RR], 2.34; 95% CI, 1.01-5.41; P = .047). In the self-controlled analyses, we observed 24 and 20 cases during the risk and control period, respectively. Our claims-based analysis identified an increased risk in the risk window compared with the control window (RR, 2.84; 95% CI, 1.53-5.27; P = .001), with an attributable risk of 3 per million RZV doses (95% CI, 0.62-5.64). Our medical record–based analysis confirmed this increased risk (RR, 4.96; 95% CI, 1.43-17.27; P = .01).

Conclusions and Relevance  Findings of this case series cohort study indicate a slightly increased risk of Guillain-Barré syndrome during the 42 days following RZV vaccination in the Medicare population, with approximately 3 excess Guillain-Barré syndrome cases per million vaccinations. Clinicians and patients should be aware of this risk, while considering the benefit of decreasing the risk of herpes zoster and its complications through an efficacious vaccine, as risk-benefit balance remains in favor of vaccination.

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