Major Finding: Fluzone High-Dose influenza vaccine was more immunogenic and reactogenic than the standard dose in adults aged 65 years and older.
Data Source: Phase III, multicenter, randomized, double-blind study of 3,876 participants.
Disclosures: The study was funded by Sanofi-Pasteur.
ATLANTA — Fluzone High-Dose vaccine was significantly more immunogenic than standard-dose influenza vaccine in a study of 3,876 individuals aged 65 years or older.
Sanofi-Pasteur's Fluzone High-Dose was licensed last December for use in that age group. In the phase III, multicenter, double-blind study, the participants were randomized in a 2:1 ratio to receive either high-dose (HD) vaccine containing 60 mcg hemagglutinin per strain or standard dose (SD) with 15 mcg hemagglutinin per strain. Blood specimens were obtained before vaccination and on day 28 for evaluation of influenza antibodies. Safety data were collected by diary card at 1-week and 4-week visits, and by telephone for up to 6 months after vaccination, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.
Reported injection site reactions within 7 days of vaccination were more common with HD. Pain was reported by 36% of the 2,573 participants who were assessed after receiving the HD vaccine and in 24% of the 1,260 in the SD group. Grade III pain was uncommon in both groups (0.3% with HD and 0.2% with SD). Erythema occurred in 15% with HD and 11% with SD, and swelling in 9% and 6%, respectively. Grade III erythema and swelling occurred in less than 2% of both groups. Most injection site reactions were mild to moderate and resolved within 3 days, said Dr. Greenberg, Sanofi-Pasteur's senior director of scientific and medical affairs.
Rates of systemic reactions were similar between the HD and SD groups, including myalgia (21% HD, 18% SD), malaise (18%, 14%), headache (17%, 14%), and fever (0%, 0.1%). Adverse events in the 30 minutes following vaccination were comparable (about 0.3% in both groups), as were rates of unsolicited adverse events within 28 days post vaccination (22% of both groups) (J. Infect. Dis. 2009;200:172-80).
Only two serious adverse events were reported by investigators as being vaccine-related: an exacerbation of Crohn's disease 2 days after receipt of HD vaccine, and a new diagnosis of myasthenia gravis 1 month after SD vaccination.
To satisfy requirements of the Food and Drug Administration, Fluzone was required to demonstrate superiority to SD vaccine for at least two of the three vaccine influenza strains, without inferiority for any strain. Fluzone achieved superiority—as determined by significantly greater geometric mean antibody titers—for the H1N1 and H3N2 strains and noninferiority for the B strain. The HD/SD geometric mean antibody titer ratios were 1.7 for H1N1, 1.8 for H3N2, and 1.3 for B, Dr. Greenberg reported.
The differences in immunogenicity were maintained for persons younger than 75 years vs. those 75 and older, for those with or without a history of cardiovascular or respiratory disease, and for both males and females, he added.
Sanofi-Pasteur began a 3-year randomized, blinded postlicensure efficacy trial of Fluzone High-Dose in September 2009. The vaccine will be available for the 2010-2011 flu immunization season.