Reduced risks of influenza-associated hospitalization and complications following vaccination among over 2 million older individuals: a nationwide study using target trial emulation framework

Abstract Background Current evidence on influenza vaccine effectiveness (VE), which is predominately derived from small high-risk older populations and focuses on specific influenza-related complications, might not be generalizable to real-world older populations with diverse characteristics in Taiwan. Therefore, this observational study with a target trial emulation framework aimed to evaluate the clinical effectiveness of an influenza vaccine on influenza infection, complications, and associated healthcare utilization and costs. Methods 1,214,392 propensity-score-matched pairs of vaccinated and unvaccinated older populations from the influenza season of 2018/2019 were identified from Taiwan’s National Health Insurance Research Database. VE (estimated as 1 minus hazard ratio [HR]*100%) and the HRs were used for influenza events and associated complications, respectively. Results Primary analyses show 14% (10–18%) of VE against influenza-associated hospitalization, irrespective of age, frailty status, and underlying influenza risk. Notably, a decline in VE for influenza-associated hospitalization was observed when the observational period following vaccination was extended (25% [19–30%], 23% [18–28%], and 14% [10–18%] for the intervals October 2018–March 2019, October 2018–May 2019, and October 2018–September 2019, respectively). Compared with non-vaccination, having an influenza vaccination significantly reduced risks of influenza-associated death by 30%, various respiratory by 12–26%, cardiovascular complications by 39–47%, and acute kidney injury by 23%. Approximately savings of USD 3,000,000 in total from averting influenza-associated hospitalization following vaccination were found. The non-significant effects of the influenza vaccine on negative control outcomes support the validity of the study procedures. Conclusions VE for severe influenza events (i.e., those requiring hospitalization) and related complications among the real-world older population was corroborated. To avoid severe influenza episodes and complications and minimize associated economic consequences, continuous influenza vaccine uptake over different influenza seasons is recommended for this population.