High-Dose Flu Vaccine More Effective for Patients on Dialysis

Troy Brown, RN

October 24, 2018

Patients on dialysis who received a high-dose influenza vaccine were less likely to be hospitalized for any reason compared with those who received a standard-dose vaccine, a large study found.

"We found that the administration of the high-dose influenza vaccine was associated with 8% fewer first hospitalizations than the standard-dose vaccine in 2016-17. In 2015-16 there was no difference by vaccine type although statistical power was limited, with only 8% of patients receiving high dose that year, compared with 61% in 2016-17," first author Dana C. Miskulin, MD, from the Division of Nephrology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, said in a news release.

The study was published online October 23 in Clinical Journal of the American Society of Nephrology.

High-dose influenza vaccine contains four times more antigen per strain than the standard-dose vaccine. Research suggests it is more effective in older adults, who often have a weaker response to the standard vaccine than younger individuals. The Centers for Disease Control and Prevention recommends that clinicians consider it for older individuals.

Similarly, studies have shown that immune response to the influenza vaccine is weaker among patients on dialysis compared with same-aged adults in the general population. Therefore, Miskulin and colleagues wanted to determine whether the high-dose vaccine could be of benefit to this population as well.

They compared the rate of hospitalizations and deaths by vaccine type (standard trivalent, standard quadrivalent, and high-dose trivalent influenza vaccine) during the 2015-16 and 2016-17 influenza seasons using data from a not-for-profit dialysis provider with approximately 230 US clinics. The patients were receiving maintenance in-center hemodialysis (HD) or peritoneal dialysis (PD) and had been vaccinated against influenza at their dialysis clinic. The researchers adjusted for age, race, cause of end-stage renal disease (ESRD), ESRD vintage, PD vs HD, serum albumin, ESRD Seamless Care Organization, and hospitalization in the past 2 months. They stratified their analyses by age and dialysis modality.

Hospitalizations Significantly Reduced With High-Dose Vaccine in 2016

Between September and December 2016, 3614 (39%) patients received quadrivalent influenza vaccine, and 5700 (61%) received high-dose trivalent vaccine. Only 127 patients (fewer than 1%) received the standard trivalent vaccine during this season.

Adjusted rates of first hospitalization were 8.71 and 8.04 per 100 patient-months for quadrivalent and high-dose trivalent vaccine, respectively. Hospitalizations were significantly reduced among those who received the high-dose vaccine (hazard ratio, 0.93; 95% confidence interval, 0.86 - 1.00; P = .04).

"When examined by age group, the protective effect of HD-IIV3 [high-dose trivalent vaccine] was observed only among adults 65 years of age or older, though an interaction term for age and vaccine type was nonsignificant in analysis," Megan C. Lindley, MPH, and David K. Kim, MD, from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, write in an accompanying editorial.

Receipt of the high-dose vaccine in 2016 was not significantly associated with adjusted all-cause mortality rates, which were 0.98 and 1.02 for standard-dose quadrivalent and high-dose trivalent vaccine, respectively. "There was no significant heterogeneity of either association by age group or dialysis modality," the authors write.

No Significant Differences in 2015-16 Flu Season

During the fall of 2015, 9843 patients received influenza vaccine: 3057 (31%) received standard-dose trivalent vaccine, 5981 (61%) received standard-dose quadrivalent vaccine, and 805 (8%) received high-dose trivalent vaccine. There were no significant differences between vaccine types for adjusted rates of first hospitalization or death during the 2015-16 influenza season.

The adjusted rates of first hospitalization according to vaccine type were 8.43, 7.88, and 7.99 per 100 patient months for standard-dose trivalent, standard-dose quadrivalent, and high-dose trivalent vaccines, respectively. Adjusted mortality rates were 1.00, 0.97, and 1.04, respectively. There were no significant differences in adjusted models of the full cohort or in age-stratified analyses for time to first hospitalization, death, or time to a composite of first hospitalization or death. The findings did not differ between patients treated with PD compared with patients receiving HD.

Lindley and Kim say they are not surprised that there were no differences in effectiveness between the standard quadrivalent and high-dose trivalent vaccines during the 2015-2016 season, given the small proportion of patients who received the high-dose vaccine that season. In addition, "the substantial variability in timing and severity of seasonal influenza epidemics and types of influenza viruses that predominate commonly poses limitations for influenza vaccination research and underscores the need for studies that gather data in multiple locations over multiple influenza seasons," they explain.

"The 2015-2016 influenza season started and peaked late, and was milder than the three previous seasons, while the 2016-2017 season was moderately severe. These factors may partially explain why vaccine type effects were observed among older dialysis patients in 2016-2017 but not in 2015-2016," they continue.

"Despite the reduction in hospitalizations observed in 2016-2017, no effect of high-dose influenza vaccination on all-cause mortality was seen in the study population in either study year. Although all-cause mortality is a non-specific outcome, overall estimates of excess mortality attributable to influenza suggest a significant annual burden of influenza disease in the United States, and presumably many of the over 900 deaths in the study population each season were influenza-related," Lindley and Kim write in their editorial.

Lindley and Kim explain that additional studies of the effect of high-dose influenza vaccine on influenza-associated mortality among patients on dialysis are urgently needed in light of the fact that these patients — especially those aged 65 years and older — have a significantly higher risk for influenza complications, including death.

"Additional studies of other strategies to increase influenza vaccine effectiveness in dialysis patients and other immunocompromised populations, including the use of adjuvants and booster doses, could also be beneficial. Even in the absence of increased vaccine effectiveness, improvements in influenza vaccination coverage among medically vulnerable populations such as dialysis patients could increase protection against influenza. In groups where the burden of influenza disease and its complications are disproportionately felt, small improvements in vaccine effectiveness and vaccination coverage may have large impacts," Lindley and Kim conclude.

The authors and editorialists have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online October 23, 2018. Abstract, Editorial

For more news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.