A recent article published by Butler et al in AJKD examines the comparative effectiveness of standard versus high-dose influenza vaccine in the dialysis population. Social Media Editor, Dr. Timothy Yau (AJKDBlog), interviews Dr. Anne Butler (AB) on their nonexperimental study.

AJKDBlog: One of the most important things I feel I can do as a clinician during flu season is to vaccinate my patients who have kidney disease. Why is this important for the population you studied, and what data are out there already?

AB: Influenza vaccination in the dialysis population is particularly important because these patients are at increased risk for severe complications from flu. But existing recommendations do not currently state a preference for the type of vaccine that should be administered in the dialysis population. Several vaccine formulations that use advanced technologies have been licensed in recent years, but there is limited knowledge about the effectiveness and safety of these vaccines in the dialysis population. Adjuvanted and high-dose formulations are licensed for use in adults ≥ 65 years.

AJKDBlog: The high-dose and standard-dose vaccine protect against the same 3 strains. However, the high dose has 4x as much antigen as the standard dose to induce a higher antibody response. Why is this particularly significant in hemodialysis patients?

AB: Patients with end-stage kidney disease (ESKD) have an impaired innate and adaptive immune system which contributes to increased risks for severe complications from influenza. Standard-dose influenza vaccines have been shown to be ineffective or minimally effective for influenza prevention in patients receiving dialysis. Since the high-dose vaccine elicits greater antibody responses than the standard-dose vaccine in patients receiving dialysis, we wanted to know whether this would translate to better influenza prevention as measured by clinical outcomes.

AJKDBlog: Flu prevalence changes year to year, as does the predominant strain. Your study looked at yearly cohorts over several flu seasons (2010-2015). Did you find large variations in the yearly cohorts with regards to your primary outcome (all-cause mortality, hospitalization for influenza, influenza-like illness)?

AB: Yes, our study period of five influenza seasons included a range of seasonal influenza severity (1 low, 2 moderate, and 2 high seasons) as measured in the overall population of older adults in the United States. These severity metrics correlated with the observed risk of clinical outcomes in our analyses. It is also noteworthy that the predominant strain and the serologic vaccine match likely influenced the seasonal variation in our observed clinical outcomes. Influenza A (H3N2) was the predominant strain during 4 of the 5 seasons, whereas only one season had influenza A (H1N1) as the predominant strain. Also, the serologic vaccine match was relatively high during 4 of the 5 seasons (ie, 97%, 80%, 86%, 95% and 40%), indicating similarity between the influenza viruses in the vaccine and circulating in the community.

Image from CDC Public Health Image Library / Dan Higgins

AJKDBlog: Out of the more than 250,000 patients, fewer than 3% received a high-dose vaccine. Were you surprised at this low incidence?

AB: The high-dose vaccine was licensed by the US Food and Drug Administration in December 2009. It has had slow but increasing uptake in the dialysis population. Many dialysis clinics make decisions regarding which vaccines they will or will not offer based on a variety of factors, including cost, availability, effectiveness, and safety. The types of vaccines administered to patients in the clinic are then limited by the formulary decisions made by each dialysis clinic. During the 2010-2015 study period, it is likely that many private dialysis facilities did not include the high-dose influenza vaccine on their formulary. But, the uptake of the high-dose vaccine increased substantially in the dialysis population in the fall of 2016. As our study ended in 2015, this accounts for the relatively low rate of high-dose vaccine use.

AJKDBlog: Because so many more patients received standard-dose vaccines, I found it easier to look at your results based on percent. There did not appear to be major differences in rates between any of the primary outcomes between the two groups. Can you expand on the big takeaway on your results?

AB: We observed similar risks for all-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness among dialysis patients who received high-dose vaccine compared with those who received standard-dose vaccine, indicating that the high-dose vaccine did not appear any more effective than standard-dose vaccine. Our findings were generally consistent across subgroups of influenza season (2010/2011 to 2014/2015), age group (<65, 65-74, 75-84, ≥85 years), years on dialysis (<1, 1-2, 3-4, 5-9, ≥10 years), timing of influenza vaccination (August/September, October, or later), and valence of standard-dose vaccine (trivalent, quadrivalent). Our results also accounted for individual-level and dialysis facility-level differences between high-dose and standard-dose vaccine recipients.

Table 2 from Butler et al, AJKD © National Kidney Foundation.

AJKDBlog: You mention the cost trade-off, $33 more for high-dose. When expanded to the population level, the cost would be substantial. Based on your data, is there any support for using high-dose influenza vaccines for dialysis patients?

AB: Recommendations for vaccine formulations ought to consider a variety of factors including effectiveness, safety, cost, and availability. Our study of patients on dialysis suggests that the high-dose vaccine does not provide additional benefit beyond the standard-dose vaccine on a population level. Our work to evaluate the safety of the high-dose vs standard-dose vaccine is ongoing. Given the substantial burden of influenza-related morbidity and mortality in the dialysis population, patients on dialysis should continue to receive annual influenza immunization per CDC guidelines. Future studies of alternative strategies (eg, booster doses) and alternative vaccine production technologies (eg, adjuvanted or cell-based vaccines) are warranted because there remains a need for improved influenza prevention efforts in this population. 

AJKDBlog: Thank you so much for taking the time to do this interview!

To view Butler et al (subscription required), please visit AJKD.org.

Title: Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis
Authors: A.M. Butler, J. Layton, V.R. Dharnidharka, J.M. Sahrmann, M.J. Seamans, D.J. Weber, and L.J. McGrath
DOI: 10.1053/j.ajkd.2019.05.018