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Risk of gout flares after vaccination: a prospective case cross-over study
  1. Chio Yokose1,
  2. Natalie McCormick1,2,
  3. Clara Chen3,
  4. Tuhina Neogi4,
  5. Christine Chaisson3,
  6. Robert Terkeltaub5,
  7. David J Hunter6,
  8. Yuqing Zhang1,
  9. Hyon Choi1,2,7
  1. 1 Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
  2. 2 Arthritis Research Centre of Canada, Richmond, Virginia, Canada
  3. 3 Data Coordianting Center, Boston University, Boston, Massachusetts, USA
  4. 4 Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, Massachusetts, USA
  5. 5 Rheumatology, UCSD/ VA Medical Center, San Diego, California, USA
  6. 6 Rheumatology, University of Sydney, St Leonards, New South Wales, Australia
  7. 7 Division of Rheumatology, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Hyon Choi; HCHOI{at}


Objectives The recombinant zoster vaccine (RZV) containing a strong non-aluminium adjuvant is associated with increased risk of gout flares, presumably via NLRP3 inflammasome activation. We tested the possibility that other vaccines may also be associated with gout flares.

Methods We conducted an online case-crossover study of patients with gout to examine the association between vaccination and gout flares. We collected information through the Internet on exposures to potential risk factors, including vaccinations, during 2-day hazard periods prior to gout flare and 2-day control periods without a flare. Conditional logistic regression was used to adjust for covariates.

Results There were 517 participants with gout (mean age 55 years, 79% male) who experienced gout flares during follow-up. There were 28 vaccinations during 990 hazard periods and 21 vaccinations during 1407 control periods. Vaccination was associated with twofold higher odds of gout flare (adjusted OR 1.99; 95% CI 1.01 to 3.89).

Conclusion Our findings suggest vaccines other than RZV are associated with increased odds of gout flares, potentially through a shared pathogenetic mechanism like NLRP3 inflammasome. However, the absolute magnitude of increased odds of gout flares with vaccinations remains small and must be interpreted within the context of the overwhelming benefits of vaccinations.

  • case-crossover study
  • gout
  • vaccination

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  • Handling editor Josef S Smolen

  • Contributors TN, YZ, HC contributed to study design. CC, TN, CEC, YZ and HC contributed to study conduct. CY, NM, YZ and HC contributed to study analysis. All authors contributed to interpretation of results. CY and HC drafted the manuscript, and all authors reviewed and revised the manuscript for content.

  • Funding This study was supported by the National Institutes of Health [P60 AR047785]. CY is supported by Ruth L Kirschstein Institutional National Research Service Award [T32-AR-007258]. NM is supported by a Fellowship Award from the Canadian Institutes of Health Research. RT is supported by the National Institutes of Health [AR060772] and VA Research Service [I01BX001660]. DJH is supported by an NHMRC practitioner fellowship. TN was supported by [K24 AR070892] for this work. HKC is supported by the National Institutes of Health [AR060772].

  • Disclaimer RT consultant to SOBI, Horizon and Selecta. DJH consultant to TLC Bio, Pfizer, Lilly, Merck Serono. TN consultant to (all unrelated to this study) Pfizer, EMD, Merck Serono, Regeneron, Novartis. HKC reports research support from AstraZeneca, and consultant to Takeda, Selecta, GSK and Horizon (all less than $10 000).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Boston University Medical Center Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available.