Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis

Abstract

Rationale & objective: Studies of patients on maintenance dialysis therapy suggest that standard-dose influenza vaccine (SDV) may not prevent influenza-related outcomes. Little is known about the comparative effectiveness of SDV versus high-dose influenza vaccine (HDV) in this population.

Study design: Cohort study using data from the US Renal Data System.

Setting & participants: 507,552 adults undergoing in-center maintenance hemodialysis between the 2010 to 2011 and 2014 to 2015 influenza seasons.

Exposures: SDV and HDV.

Outcomes: All-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness during the influenza season.

Analytic approach: Patients were eligible for inclusion in multiple yearly cohorts; thus, our unit of analysis was the influenza patient-season. To examine the relationship between vaccine dose and effectiveness outcomes, we estimated risk differences and risk ratios using propensity score weighting of Kaplan-Meier functions, accounting for a wide range of patient- and facility-level characteristics. For nonmortality outcomes, we used competing-risk methods to account for the high mortality rate in the dialysis population.

Results: Within 225,215 influenza patient-seasons among adults 65 years and older, 97.4% received SDV and 2.6% received HDV. We observed similar risk estimates for HDV and SDV recipients for mortality (risk difference, -0.08%; 95% CI, -0.85% to 0.80%), hospitalization due to influenza or pneumonia (risk difference, 0.15%; 95% CI, -0.69% to 0.93%), and influenza-like illness (risk difference, 0.00%; 95% CI, -1.50% to 1.08%). Our findings were similar among adults younger than 65 years, as well as within other subgroups defined by influenza season, age group, dialysis vintage, month of influenza vaccination, and vaccine valence.

Limitations: Residual confounding and outcome misclassification.

Conclusions: The HDV does not appear to provide additional protection beyond the SDV against all-cause mortality or influenza-related outcomes for adults undergoing hemodialysis. The additional cost and side effects associated with HDV should be considered when offering this vaccine. Future studies of HDV and other influenza vaccine strategies are warranted.

Keywords: Comparative effectiveness; end-stage renal disease (ESRD); hemodialysis; high-dose influenza vaccine; hospitalization; immunization; infection; influenza; influenza-like illness (ILI); mortality; renal dialysis; standard-dose influenza vaccine; vaccination; vaccine effectiveness.

Figure 1.

Study design schematic of inclusion criteria and follow-up time for each yearly cohort of adult patients undergoing maintenance hemodialysis. The index date was anchored on the date of influenza vaccination, which was required to be administered prior to the start date of the influenza season. Follow-up began on the start date of the influenza season.

Figure 2.

Cumulative risk and 95% confidence interval estimates of mortality, hospitalization for pneumonia or influenza, and influenza-like illness, accounting for the competing risk of death (for non-mortality outcomes), pooled across five influenza seasons (2010/11, 2011/12, 2012/13, 2013/14, 2014/2015). Cumulative risk was estimated using standardized mortality ratio-weighted Kaplan-Meier functions. The scales of the y-axes differ by outcome.

Figure 3.

The risk of mortality among patients who received the high-dose versus standard-dose influenza vaccines, by subgroup. Risk differences were calculated as the difference between weighted cumulative risk functions, with bootstrap confidence intervals. Analyses were performed in adults ≥65 years, with the exception of the age stratified analyses. Abbreviations: CI, confidence interval; HDV, high-dose vaccine; SDV, standard-dose vaccine.

Figure 4.

The risk of hospitalization due to influenza / pneumonia among patients who received the high-dose versus standard-dose influenza vaccines, by subgroup. Risk differences were calculated as the difference between weighted cumulative risk functions, accounting for the competing risk of death, with bootstrap confidence intervals. Analyses were performed in adults ≥65 years, with the exception of the age stratified analyses. Abbreviations: CI, confidence interval; HDV, high-dose vaccine; SDV, standard-dose vaccine.

Figure 5.

The risk of influenza-like illness among patients who received the high-dose versus standard-dose influenza vaccines, by subgroup. Risk differences were calculated as the difference between weighted cumulative risk functions, accounting for the competing risk of death, with bootstrap confidence intervals. Analyses were performed in adults ≥65 years, with the exception of the age stratified analyses. Abbreviations: CI, confidence interval; HDV, high-dose vaccine; SDV, standard-dose vaccine.