PT  - JOURNAL ARTICLE
AU  - Kiely, Marilou
AU  - Tadount, Fazia
AU  - Lo, Ernest
AU  - Sadarangani, Manish
AU  - Wei, Shu Qin
AU  - Rafferty, Ellen
AU  - Quach, Caroline
AU  - MacDonald, Shannon E
TI  - Sex differences in adverse events following seasonal influenza vaccines: a meta-analysis of randomised controlled trials
AID  - 10.1136/jech-2023-220781
DP  - 2023 Dec 01
TA  - Journal of Epidemiology and Community Health
PG  - 791--801
VI  - 77
IP  - 12
4099  - http://jech.bmj.com/content/77/12/791.short
4100  - http://jech.bmj.com/content/77/12/791.full
SO  - J Epidemiol Community Health2023 Dec 01; 77
AB  - Background Despite being a vaccine-preventable disease, influenza remains a major public health threat with vaccine safety concerns reducing vaccine acceptability. Immune responses to vaccines and adverse events may differ between males and females, but most studies do not report results by sex. Using data from clinical trials, we explored sex differences in adverse events following seasonal influenza vaccines.Methods We obtained data for phase III randomised controlled trials identified through a systematic review and clinical trials registries, and performed a two-stage meta-analysis. Risk ratios (RR) and 95% confidence intervals (95% CI) comparing solicited reactions in females versus males were pooled using the Mantel-Haenszel method and a random-effects model. We used the ROBINS-I tool to assess risk of bias and the I2 statistic for heterogeneity. Main analysis was stratified by age: 18–64 years and ≥65 years.Results The dataset for this analysis included 34 343 adults from 18 studies (12 with individual-level data and 6 with aggregate data). There was a higher risk of injection site reactions in females compared with males for both younger and older participants, with RRs of 1.29 (95% CI 1.21 to 1.37) and 1.43 (95% CI 1.28 to 1.60), respectively. Higher risk in females was also observed for systemic reactions, with RRs of 1.25 (95% CI 1.20 to 1.31) and 1.27 (95% CI 1.20 to 1.34) for younger and older participants, respectively. We also observed elevated risks of severe reactions in females, with a higher RR in younger versus older participants for systemic reactions (RRs 2.12 and 1.48, p=0.03, I2=79.7%). RRs were not found to vary between quadrivalent and trivalent vaccines.Conclusion This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine type. Transparent communication of this risk could increase the trust in vaccines and limit vaccine hesitancy. Future studies should report results stratified by sex and explore the role of gender in the occurrence of adverse events.Data may be obtained from a third party and are not publicly available.