High-dose influenza vaccination in the elderly

On December 23, 2009, the Food and Drug Administration (FDA) approved a new high-dose seasonal influenza vaccine designed for adults 65 years or older. Fluzone High-Dose (sanofi pasteur), approved through the accelerated-review pathway, contains 60 mcg hemagglutinin (HA) antigen from each of the three influenza strains, which is four times the amount of each antigen in traditional injectable seasonal influenza vaccines. Preventing influenza in patients 65 years or older is an area of interest because of the rapid increase in the number of individuals in this patient group and the fact that the group accounts for up to 90% of influenza-related mortality.1,2 However, the protective efficacy of the traditional inactivated influenza vaccine appears to be much lower in elderly adults compared with younger adults.3 Studies have shown that, in general, after age 65 years, individuals have a lower response rate to inactivated influenza vaccine based on hemagglutination inhibition (HAI) titers.4,5 It is hypothesized that the aging immune system is considerably less able to mount an adaptive immune response, which impairs the body’s ability to make antibodies when exposed to a vaccine. One approach to improve antibody responses to influenza vaccine in elderly individuals is to increase the dose of antigen. Keitel et al.6 showed dose-related increases in HAI antibody responses in 202 medically stable ambulatory patients older than 65 years. The maximum dose of HA used in the trial was 60 mcg per strain. In patients with low preimmunization antibody titers, responses to the vaccine with 60 mcg antigen per strain compared with 15 mcg per strain nearly doubled 1 month after vaccination. Although the high-dose influenza vaccine caused an increase in the frequency of injection site reactions, the majority of those reactions were mild and transient. Couch et al.7 also compared 60 versus 15 mcg HA per strain doses using the 2004–05 seasonal vaccine in patients older than 65 years (range 65– 95). The patients were separated into two groups (one group consisting of 78% of all enrollees who had received the seasonal vaccine 2 to 5 months earlier and those who had not), then randomized into highor standarddose groups. In addition to HAI titers, neutralization tests were performed against all three component antigens. Both vaccines evoked substantial increases (defined as a fourfold increase or more in antibody titers) against all three virus strains in all four groups. The high-dose vaccine produced higher mean titers than the standard dose for all three antigens. Notably, a low percent of patients reached this greaterthan-fourfold increase in titers that is considered protective. The percent of patients who developed adequate titers for HAI ranged from 16.8% to 23.6% for standard dose versus 35.0% to 51.5% for high dose. The percent reaching adequate levels of neutralizing antibody titer ranged from 16.3% to 25.0% for standard dose versus 36.9% to 43.7% for high dose. The adverse effects, though not serious (primarily pain and myalgias), were more common in the high-dose group. Another study published by Falsey et al.8 compared the immunogenicity of high-dose influenza vaccine with standard-dose influenza vaccine in adults 65 years or older. This randomized, double-blind, controlled trial of 3,837 participants reported significantly higher geometric mean HAI antibody titers (GMTs) and rates of seroconversion and seroprotection in participants who received highversus standarddose vaccine. One month after vaccination, the GMT ratio of high-dose compared with standard-dose vaccine was 1.7 for influenza subtype A/H1N1, 1.8 for subtype A/H3N2, and 1.3 for type B. High-dose vaccine met predefined superiority criteria for H1N1 and H3N2 strains and noninferiority criteria for the B strain. This study also reported higher rates of injection site reactions with the high-dose vaccine compared with the standard-dose vaccine, although they were generally not severe. The CPT (Current Procedural Terminology) code for Fluzone High-Dose has been established (90662) and described as “Influenza virus vaccine, split virus, preservative free, enhanced immunogenicity via increased antigen content, for intramuscular use.” It will be packaged as 0.5-mL prefilled syringes without needles in packages of 10. Additional information on private insurance and Medicare coverage has not been released at this time. According to sanofi pasteur officials, the vaccine will be available in the fall for the 2010–11 influenza season and will cost approximately twice as much as the seasonal vaccine (announced at February 2010 Advisory Committee on