Conference Coverage
High-dose flu vaccine immunogenic in frail elderly
Major finding: Geometric mean titers in the standard vs. high-dose group, respectively, for 2011-2012: 27.9 vs. 67.7 for A/California/07/2009; 9.3...
A high-dose influenza vaccine for elderly patients provided 24% more protection against the disease than did the standard-dose vaccine in a randomized postlicensure study.
Switching seniors to the higher-dose formulation could prevent as many as five cases of flu per 1,000 people aged 65 years and older each year, Dr. David Greenberg said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).
Fluzone High-Dose vaccine (Sanofi Pasteur) is a trivalent, inactivated, split-virus influenza vaccine that contains 16 mcg hemagglutinin per dose of each included strain (aH1N1, B, and aH3N2). This is four times more antigen than in the standard Fluzone (15 mcg/dose). The high-dose formulation was developed to induce better antibody responses in adults aged 65 years or older, in an attempt to provide better protection and avert some of the disease burden that accompanies influenza in older people.
"Older adults represent about 13% of the U.S. population, but account for 63% of the hospitalizations for influenzalike illness, and more than 80% of influenza-related deaths," Dr. Greenberg said.
The Food and Drug Administration approved the high-dose vaccine on its accelerated approval pathway in late 2009. A prelicensure phase III study was conducted in 3,600 elderly adults. The high-dose vaccine stimulated significantly more protective antibody responses against all three strains than did the corresponding regular-dose vaccine; the high-dose vaccine met the FDA superiority requirement for both A strains. The response was stable across age, sex, and the presence of comorbid conditions.
"Last year, however, only an estimated 19% of vaccinated seniors got the high-dose vaccine, largely because policy groups and providers have been waiting for the results of this postlicensure trial," Dr. Greenberg said. He reported these results – most of which came in just last week – at the meeting in Atlanta.
The postlicensure study comprised more than 32,000 persons aged 65 years and older. They were enrolled at 126 sites in the United States and Canada. The trial spanned two flu seasons (2011-2012 and 2012-2013). Participants were randomized to either one dose of the high concentration vaccine or one dose of the regular vaccine.
Over both seasons, the high-dose vaccine was an average of 24% more effective in preventing influenza-like illness from types A and B combined than the regular-dose vaccine.
That benefit was more pronounced in older subjects, Dr. Greenberg noted. Among those aged 65-74 years, the relative efficacy was almost 20%; among those aged 75 years and older, the relative efficacy was 32%. The benefit held whether the illness was defined as lab confirmed (24%) or culture confirmed (23%).
The high-dose vaccine significantly reduced the risk of pneumonia associated with laboratory-confirmed influenza by up to 53%. The risk of cardiorespiratory illness within 30 days of flu onset dropped by almost 30%, while the risk of flu-related 30-day hospital admissions fell by about 40%.
Safety outcomes were good when compared with the regular-dose vaccine, Dr. Greenberg said. Serious adverse events occurred in 8% of the high dose group and 9% of the regular-dose group.
Sanofi Pasteur will continue to analyze the study data, Dr. Greenberg said. The company intends to submit a clinical study report to the FDA’s Center for Biologics Evaluation and Research by the first quarter of next year. Sanofi will also seek a revision of the prescribing information supporting the vaccine’s clinical superiority to the regular-dose vaccine.
Dr. Greenberg is the senior director of U.S. scientific and medical affairs for Sanofi Pasteur.