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Vaccination

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

Educational Objective To evaluate the risk of developing Guillain-Barré syndrome following vaccination with zoster vaccine using Medicare claims.

1 Credit CME

JAMA Internal Medicine

Published Online: November 1, 2021

Original Investigation

Article Information and Disclosures

Ravi Goud, MD, MPH¹;

Bradley Lufkin, MPA, MSES²;

Jonathan Duffy, MD, MPH³;

Barbee Whitaker, PhD¹;

Hui-Lee Wong, PhD¹;

Jiemin Liao, MS²;

An-Chi Lo, MS, MPH²;

Shruti Parulekar, MPH²;

Paula Agger, MD, MPH¹;

Steven A. Anderson, MPP, PhD¹;

Michael Wernecke, BS²;

Thomas E. MaCurdy, PhD^2,4;

Eric Weintraub, MPH³;

Jeffrey A. Kelman, MD, MMS⁵;

Richard A. Forshee, PhD¹

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

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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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Article Information

Accepted for Publication: September 7, 2021.

Published Online: November 1, 2021. doi:10.1001/jamainternmed.2021.6227

Corresponding Author: Ravi Goud, MD, MPH, Center for Biologics Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Bldg 71, Room 1330, Silver Spring, MD 20993-0002 (ravi.goud@fda.hhs.gov).

Author Contributions: Dr MaCurdy had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Goud, Lufkin, Duffy, Liao, Lo, Parulekar, Agger, Anderson, Wernecke, Kelman, Forshee.

Acquisition, analysis, or interpretation of data: Goud, Lufkin, Duffy, Whitaker, Wong, Liao, Lo, Parulekar, Anderson, Wernecke, MaCurdy, Weintraub, Kelman, Forshee.

Drafting of the manuscript: Goud, Lufkin, Liao, Lo, Parulekar, Agger, Wernecke, Kelman.

Critical revision of the manuscript for important intellectual content: Goud, Lufkin, Duffy, Whitaker, Wong, Liao, Anderson, Wernecke, MaCurdy, Weintraub, Kelman, Forshee.

Statistical analysis: Lufkin, Liao, Lo, Parulekar, Wernecke, MaCurdy, Weintraub.

Obtained funding: Anderson, MaCurdy, Kelman, Forshee.

Administrative, technical, or material support: Goud, Lufkin, Duffy, Whitaker, Wong, Liao, Lo, Parulekar, Agger, Anderson, Wernecke, Weintraub, Kelman.

Supervision: Goud, Lufkin, Liao, Lo, Anderson, Wernecke, MaCurdy, Weintraub, Kelman, Forshee.

Conflicts of Interest Disclosures: Drs Lufkin, Liao, Lo, Parulekar, and Wernecke reported funding from Acumen, LLC during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded through an interagency agreement between the US Food and Drug Administration and the Centers for Medicare & Medicaid Services (IAA number: 244-18-1067S).

Role of the Funder/Sponsor: The US Food and Drug Administration and the Centers for Medicare & Medicaid Services had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The authors are employees or contractors of the US Food and Drug Administration, the Centers for Disease Control and Prevention, or the Centers for Medicare & Medicaid Services; however, other officials at the US Food and Drug Administration, the Centers for Disease Control and Prevention, and the Centers for Medicare & Medicaid Services had no role in the design and conduct of the study; collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The manuscript was subject to administrative review before submission, but the content was not altered by this review. The views expressed are those of the authors and not necessarily those of the Department of Health and Human Services, the US Food and Drug Administration, the Centers for Disease Control and Prevention, or the Centers for Medicare & Medicaid Services.

Meeting Presentation: This work was presented in part at the Meeting of the Advisory Committee on Immunization Practices; Atlanta, Georgia, June 26, 2019.

Additional Contributions: We thank Manzi Ngaiza, MPH, Sam Shangguan, MPH, and Yoganand Chillarige, MPA, Acumen LLC, for their support with analytics, coordination, and manuscript drafting and review.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.