1D-03 - Recombinant Zoster Vaccine and Risk of Incident Guillain-Barré Syndrome in US Adults ≥ 65 Years of Age

Background: Post-licensure evaluations identified an increased risk of Guillain-Barré syndrome (GBS) with the recombinant zoster vaccine (RZV). Studies using real-world data are critical for generating real-world evidence of vaccine safety in large populations.

Objectives: To evaluate the risk of incident GBS following RZV exposure among US Medicare beneficiaries ≥65 years old.

Methods: A self-controlled risk interval case-only design evaluated incident GBS in the 1-42-day risk window (RW) relative to the 43-84-day control window (CW) following RZV exposure. The case-only design included individuals who experienced incident GBS in either the RW or the CW after RZV dose 1 or dose 2. The analytic cohort of US Medicare beneficiaries ≥65 years-old enrolled in Medicare fee-for-service Parts A, B, and D who received at least one RZV dose from 2018 to 2020 was identified from Medicare administrative claims (i.e., inpatient, outpatient, and physician offices, and pharmacy dispensed prescriptions). Using a validated algorithm, we identified incident GBS based on an International Classification of Disease 10th Revision diagnosis code of G61.0 in the primary position in an inpatient setting or a diagnosis in any other setting followed by an inpatient encounter within 7 days and no evidence of GBS in the 365 days preceding the incident event. Conditional Poisson regression models estimated the relative risk (RR) of incident GBS. The primary analysis did not distinguish between doses. Sensitivity analyses tested dose-specific effects, 60-183-day dose spacing per US label, impact of the COVID-19 pandemic, and seasonality. We report the RR and attributable risk (AR) with corresponding 95% confidence intervals (CI).

Results: Among 3,383,799 individuals ≥65 years-old who received RZV and met the study inclusion criteria, we identified 75 incident GBS cases. Most (n=57) cases occurred in the RW, and 18 occurred in the CW. The primary analysis without distinguishing doses revealed a RR=3.15 (95% CI: 1.82, 5.68) and AR=6.59 per 1,000,000 doses (95% CI: 4.35, 7.96). For the dose-specific analysis, we detected a statistically significant increased risk after dose 1 (RR= 5.33; 95% CI: 2.59, 12.36) but not dose 2. An increased risk was also detected in the sensitivity analyses to assess the impact of the COVID-19 pandemic and seasonality. The 60-183-day dose spacing analysis that included 20 cases, most of which were after dose 2, did not show a statistically significant increased risk.

Conclusions: An increased risk of incident GBS was detected among US adults ≥65 years-old enrolled in Medicare who received RZV. The findings detected an increased risk of incident GBS after RZV dose 1 but not dose 2.