Comparative Postmarket Safety Profile of Adjuvanted and High-Dose Influenza Vaccines in Individuals 65 Years or Older

Importance Every year, influenza vaccines are administered to millions of people worldwide to reduce morbidity and mortality from influenza. As new vaccine formulations are increasingly used, monitoring and comparing safety, in addition to vaccine effectiveness, in target populations are essential. Objective To assess the postmarketing safety profile of 2018 Southern Hemisphere influenza vaccines, particularly 2 new enhanced trivalent inactivated influenza vaccines: an adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose trivalent inactivated influenza vaccine (HD-IIV3), among Australian individuals 65 years or older. Design, Setting, and Participants This cohort study used solicited short message service-based self-reported survey data on adverse events occurring within 3 to 5 days after receipt of an influenza vaccination. Participants included individuals 65 years or older who received routinely recommended influenza vaccines at 1 of 265 sentinel immunization sites, including primary care, hospital, and community-based clinics, participating in Australia's AusVaxSafety active vaccine safety surveillance system from April 1 to August 31, 2018. Data were analyzed from September 1, 2018, to June 30, 2019. Exposure Any licensed 2018 influenza vaccine administered in clinical practice. Main Outcomes and Measures Rates (overall, by brand, and by concomitant vaccine receipt) of adverse events, including medical attendance as a proxy for serious adverse events. Results Of 72 & x202f;013 individuals 65 years or older who received an influenza vaccine in 2018, 50 & x202f;134 individuals (69.6%) responded to the initial survey regarding adverse events experienced after vaccination (median [interquartile range] age, 71 [68-76] years; 27 & x202f;056 [54.0%] women). Most individuals received an enhanced trivalent inactivated influenza vaccine, including 28 & x202f;003 individuals (55.9%) who received aIIV3 and 19 & x202f;306 individuals (38.5%) who received HD-IIV3; 2208 individuals (4.4%) received a quadrivalent inactivated influenza vaccine. Individuals who received HD-IIV3 reported significantly higher rates of any adverse event compared with individuals who received aIIV3 (1716 individuals [8.9%] vs 1796 individuals [6.4%]; P < .001) as well as specific adverse events, including fever (195 individuals [1.1%] vs 164 individuals [0.6%]; P < .001), injection site pain (383 individuals [2.1%] vs 350 individuals [1.3%]; P < .001), and injection site swelling or redness (256 individuals [1.4%] vs 248 individuals [0.9%]; P < .001). Adverse event rates reported by those receiving any quadrivalent inactivated influenza vaccine were similar to rates reported by those receiving aIIV3. Rates of medical care seeking for adverse events associated with aIIV3 and HD-IIV3 were low and comparable (80 individuals [0.3%] vs 56 individuals [0.3%]; P = .91). Conclusions and Relevance The findings of this large-scale participant-based postmarketing assessment of the safety of 2 new enhanced influenza vaccines used in individuals 65 years or older provide reassuring near-real-time and cumulative data to inform and support confidence in ongoing vaccine use. This cohort study examines rates of adverse events following vaccinations among Australian adults 65 years or older who received influenza vaccines in 2018. Question Were the 2018 adjuvanted trivalent inactivated influenza vaccine (TIIV) and high-dose TIIV associated with adverse events in Australian individuals 65 years or older? Findings In this cohort study of active safety surveillance system data including 50 & x202f;134 adults 65 years or older who responded to a short messaging service-based survey of self-reported adverse events following immunization, 94.4% of participants received an adjuvanted TIIV or high-dose TIIV. Individuals who received a high-dose TIIV reported higher rates of select adverse events, including fever and injection site reactions, but rates of seeking care were low and did not differ between enhanced vaccine groups. Meaning The findings of this postmarketing active sentinel surveillance system study consisting of self-reported adverse events following immunization suggest that these 2 new enhanced influenza vaccines were well tolerated among an older Australian population.