Comparative Effectiveness of Different Influenza Vaccine Formulations among Patients Undergoing Maintenance Hemodialysis

BACKGROUND: Influenza vaccination is recommended to prevent influenza in patients with kidney failure. It remains unclear whether newer, enhanced vaccine formulations are more effective than standard-dose, egg-based, inactivated influenza vaccine (standard-dose vaccine) in patients undergoing dialysis. We sought to compare the effectiveness of five influenza vaccine formulations among patients undergoing dialysis. METHODS: Using the United States Renal Data System database, we performed an active comparator cohort study among adults ≥65 years with kidney failure undergoing hemodialysis (2011/12 to 2019/20 influenza seasons) who received a standard-dose, high-dose, cell culture-based, adjuvanted, or recombinant influenza vaccine within a given season. We compared the risk of influenza-like illness, influenza, influenza-related hospitalization, severe influenza, and all-cause mortality during the influenza season by vaccine formulation. Season-specific risk differences and relative vaccine effectiveness (rVE) were estimated using propensity score-weighted Kaplan-Meier functions, accounting for the competing risk of death (for non-mortality outcomes). We combined the season-specific estimates via a random effects meta-analysis. RESULTS: 578,232 influenza patient-seasons included standard-dose vaccine (n=372,907), high-dose vaccine (n=192,880), cell culture-based vaccine (n=8,177), adjuvanted vaccine (n=3,308), or recombinant vaccine (n=960). Season-specific and meta-analytic estimates were consistent with a modest protective effect of high-dose vaccine versus standard-dose vaccine for influenza (meta-analytic rVE 5.1%; 95% CI, -0.7% to 10.5%), influenza-related hospitalization (meta-analytic rVE 5.5%; CI, -1.8% to 12.3%), and severe influenza (meta-analytic rVE 13.7%; CI, -9.7% to 32.1%), but not influenza-like illness or mortality. Patterns were similar for cell culture-based vaccine versus standard-dose vaccine (e.g., meta-analytic rVE for influenza, 18.3%; CI, 2.2% to 31.7%). Estimates for adjuvanted or recombinant versus standard-dose vaccines were imprecise. Quantitative bias analyses did not indicate residual confounding, although some estimates were imprecise. CONCLUSIONS: Among older adults undergoing dialysis, high-dose vaccine and cell culture-based vaccine may provide modestly increased protection versus standard-dose vaccine.