Recombinant Zoster Vaccine Not Associated with Risk of Incident Gout, Study Finds

Susan dosReis, PhD

Credit: University of Maryland, Baltimore

Findings from a recent study of US adults aged ≥ 65 years showed no statistically significant increase in the risk of incident gout following receipt of recombinant zoster vaccine (RZV).

Incident gout cases occurred equally in the risk and control windows following vaccination, with primary, secondary, and sensitivity analyses showing no association between gout and RZV exposure.¹

“In pre‑licensure clinical trials, numerical differences in gout cases between the recombinant zoster vaccine and placebo groups have been observed. However, real-world evidence is limited,” wrote investigators.¹

The US Centers for Disease Control and Prevention recommends 2 doses of RZV to prevent shingles and related complications in adults 50 years of age and older.² Safety data from a pair of phase 3 trials for RZV showed an increased risk of gout.^3,4 However, evidence of this association in a real-world setting is limited and requires further research.

To assess the risk of incident gout following RZV exposure, Susan dosReis, PhD, co-vice chair for research in the department of practice, sciences, and health outcomes research at the University of Maryland School of Pharmacy, and a team of investigators used the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse database to implement a case-only, self-controlled risk interval design. Adults ≥ 65 years of age who were enrolled in fee-for-service Medicare Parts A, B, and D and received at least 1 dose of the 2-dose RZV regimen in 2018–2019 were enrolled in the study.¹

Investigators tracked incident gout cases in the risk window, defined as days 1-30 following vaccination, and the control window, defined as days 31-60 following vaccination. For the purpose of analysis, incident gout was classified as a gout diagnosis in an inpatient or outpatient setting followed by receipt of allopurinol, colchicine, probenecid, or febuxostat within 3 months with no prior evidence of gout diagnosis or medication in the preceding 365 days. Baseline descriptive characteristics in the 12 months up to RZV exposure included age, sex, calendar year–month of RZV vaccination, concomitant preventive immunizations, comorbidities, and health care service utilization.¹

Conditional Poisson regression models were used to estimate the relative risk (RR) of incident gout following any RZV dose in a primary and secondary analysis. Sensitivity analyses included a 2-dose recipient subgroup with 60–183-day dose spacing, dose 1- and dose 2-specific analysis, a seasonality-adjusted analysis, and a COVID-19 sensitivity analysis excluding incident gout cases on or after December 2, 2019. Investigators used a temporal scan to test for significant clustering of incident gout cases after vaccination.¹

The initial search yielded 2371388 adults aged ≥ 65 years enrolled in fee-for-service Medicare Parts A, B, and D who received at least 1 dose of RZV. After excluding patients with no evidence of gout and prevalent gout at baseline, a total of 1,309 incident gout cases were included in the study. Participants were predominantly White (87%; n = 1137), male (61%; n = 801), and aged 70–79 years (55%; n = 723). Common comorbidities included chronic kidney disease (41%; n = 531), diabetes mellitus (36%; n = 473), and ischemic heart disease (33%; n = 433).¹

Of the 1,309 incident gout cases, 1,074 (82%) received 2 RZV doses. Following the first dose, 783 incident gout cases were identified. Following the second dose, 526 incident gout cases were identified. Of note, these cases occurred equally in the risk and control windows.¹

In the primary analysis, the RR of incident gout was 1.01 (95% confidence interval [CI], 0.90-1.12). Investigators pointed out the secondary analysis and all sensitivity analyses yielded similar results. Of note, the temporal scan did not detect significant clustering of incident gout cases over the 60-day follow-up.¹

“The findings show no statistically significant increased risk of incident gout following receipt of RZV in US adults aged ≥65 years,” investigators concluded.¹

References:

1. dosReis S, Zhang C, Amill-Rosario A, et al. Incident Gout After Recombinant Zoster Vaccination in Adults Aged ≥65 Years in the USA. Arthritis Rheumatol. 2023; 75. https://acrabstracts.org/abstract/incident-gout-after-recombinant-zoster-vaccination-in-adults-aged-%e2%89%a565-years-in-the-usa/. Accessed November 20, 2023.
2. US Centers for Disease Control and Prevention. Shingles (Herpes Zoster). Shingles Home. January 24, 2022. Accessed November 20, 2023. https://www.cdc.gov/shingles/vaccination.html
3. Clinicaltrials.gov. Study to Evaluate Efficacy, Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 70 Years and Older. April 27, 2020. Accessed November 20, 2023. https://clinicaltrials.gov/study/NCT01165229
4. Clinicantrials.gov. Study to Evaluate Efficacy, Safety and Immunogenicity of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 50 Years and Older. February 10, 2021. Accessed November 20, 2023. https://clinicaltrials.gov/study/NCT01165177