Clarification regarding the statement of the association between the recombinant zoster vaccine (RZV) and gout flares

We have read with great interest the article addressing the risk of gout flares after vaccination in a case crossover study by Yokose et al .1 The authors suggest that vaccines may be associated with an increased odds of gout flares potentially via activation of the NLRP3 inflammasome. The study was conducted between 2003 and 2010 prior to the availability of the recombinant zoster vaccine (RZV); however, the authors make reference to two phase III clinical trials for RZV which, they state, demonstrated a higher risk of gout flares in the vaccine group. Even though RZV was not assessed in the study by Yokose et al , we would like to clarify this statement about RZV and gout flares. The two large pivotal phase III clinical trials, ZOSTER-006/ZOE-50 (NCT01165177) and −022/ZOE-70 (NCT01165229), that involved a total of 29 305 subjects ≥50 years of age who received at least one dose of RZV (n=14 645) or placebo (n=14 660) were designed to assess the efficacy and safety of the RZV vaccine, but not to statistically assess a potential risk of gout among RZV recipients.2–4 We confirm that the analysis of the unsolicited adverse events (AE) reported during 30 days after each vaccination showed a numerical imbalance in the reporting rate of gout. Indeed, there were 27 (0.18% (95% CI 0.12 to 0.27)) versus 8 (0.05% (95% CI 0.02 to 0.11)) (unadjusted risk rario=3.38 (95% CI 1.49 to 8.60)) subjects in the RZV and placebo groups, respectively, who experienced an AE of gout or gouty arthritis.5 However, these are …