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New developments in vaccination for patients aged 65 years and older
Influenza is a significant cause of morbidity and mortality, particularly among patients aged older than 65 years. Influenza-related mortality has been estimated at 23,000 to 51,000 deaths annually. The CDC estimates that 90% of complications from influenza occur in patients aged 65 years and older; a frequent complication is secondary pneumonia.
Pneumococcal disease encompasses pneumonia, bacteremia and meningitis due to Streptococcus pneumoniae. Invasive pneumococcal disease (IPD) is comprised of bacteremia, meningitis or infection at any other sterile site. In 2007, there were approximately 40,000 cases of IPD in the United States, resulting in 4,400 deaths. Much like influenza, the highest incidence of disease is among adults aged 65 years and older.
Fortunately, both of these diseases have effective vaccines available to protect patients. Influenza vaccination has been around since the 1940s. Since the initial development of vaccine against influenza A, we have subsequently developed trivalent and quadrivalent vaccines, high-dose vaccines and live-attenuated vaccines. Pneumococcal vaccines were first licensed in 1977. Today, the pneumococcal polysaccharide vaccine (PPSV) covers 23 serotypes, and the pneumococcal conjugate vaccine (PCV) covers 13 serotypes. However, despite the documented efficacy of these vaccines against influenza and pneumococcal disease, vaccination in the elderly remains a challenge. Recent developments in influenza and pneumococcal vaccination may lead to improvements in outcomes for this population.
High-dose influenza vaccination
Vaccination is considered the mainstay in the prevention of influenza and complications of influenza. The CDC and the Advisory Committee on Immunization Practices (ACIP) recommend routine vaccination for all patients aged 6 months and older. In particular, patients aged 65 years and older are among those considered at high risk for complications from influenza.
Despite these recommendations, evidence supporting the efficacy of influenza vaccination in elderly patients is less than ideal. A systematic review published in 2005 found that vaccination was most effective at preventing complications of influenza in elderly patients residing in long-term care facilities. The benefit of vaccination in the community was found to be modest at best. The results of a Cochrane review in 2010 cast further doubt on the matter, with the researchers concluding that the current evidence offered no guidance on efficacy or safety of influenza vaccination in patients aged 65 years and older. It has been proposed that the lack of efficacy noted in these trials may be due to a lower antibody response in elderly patients. Efforts to optimize antibody response in this population led to the development of the high-dose (HD) influenza vaccine.
Jeff Brock
Gregory Tallman
The HD influenza vaccine was approved by the FDA in 2009. It is a trivalent, inactivated influenza vaccine that provides four times the amount of hemagglutinin as the standard vaccine (60 mcg vs. 15 mcg per strain). To date, the CDC and ACIP have made no recommendation of preference for either the HD vs. standard-dose (SD) influenza vaccination. However, since the recommendations were made for the 2014-2015 influenza season, new evidence has been published that provides compelling evidence for the use of the HD vaccine in elderly patients.
In August, a study on the efficacy of the HD influenza vaccine was published in The New England Journal of Medicine. This study was a multicenter, double blind, active-comparator controlled trial examining the efficacy of the HD influenza vaccine compared with SD trivalent vaccine. The study included 31,989 patients during a 2-year period. Of these, 15,991 patients were enrolled to receive the HD vaccine. The primary endpoint was incidence of laboratory-confirmed influenza illness at least 14 days after vaccination. The study included adults aged 65 years and older without moderate or severe acute illnesses and without medical history that would contraindicate use of the study vaccines.
The results of the study showed that the use of HD influenza vaccine resulted in a significantly lower incidence of laboratory-confirmed influenza cases compared with SD influenza vaccination. The HD vaccine was statistically superior to SD vaccine for preventing protocol-defined influenza-like illness, as the lower confidence bound exceeded the FDA-defined superiority margin of +9.1%.
The researchers also conducted a predefined analysis of hemagglutinin inhibition immunogenicity of the HD vaccine compared with SD vaccine. At 28 days after immunization, the HD vaccine produced higher geometric mean titers for all vaccine strains in both study years. The HD vaccine also resulted in higher incidence of seroprotection against vaccine strains in both years. Serious adverse events occurred in 8.3% of HD vaccine patients and 9% of SD vaccine patients. This was a significant reduction in relative risk for adverse events with the HD vaccine (0.92; 95% CI, 0.85-0.99).
The results of this trial indicate a significant improvement in efficacy with the use of the HD vaccine vs. the SD vaccine. Unfortunately, there was no placebo comparison, so the true level of protection conferred by the HD vaccine must be extrapolated from other clinical data. The researchers suggested tthe overall efficacy of the HD vaccine is 50% to 60%. Another consideration is that there is no quadrivalent formulation of HD influenza vaccine, nor was the HD vaccine compared with an SD quadrivalent vaccine. Therefore, there is no data to guide a decision regarding which vaccine would be better in elderly patients. Currently, the CDC and ACIP have not made a recommendation for a specific form of influenza vaccination for elderly patients; however, the data presented here make a compelling argument for improved clinical outcomes with the HD influenza vaccine.
13-valent pneumococcal conjugate vaccine
The pneumococcal polysaccharide vaccine (PPSV23) has been the recommended vaccine worldwide for the prevention of invasive pneumococcal disease in several populations, including the elderly and adults with immunocompromising conditions. This recommendation began to change in 2010 with the approval of the 13-valent conjugate vaccine (PCV13) in adults aged 50 years and older. In 2012, the ACIP recommended that PCV13 be used in all adults aged 19 years and older with immunocompromising conditions. This recommendation was based on immunogenicity data as no clinical trial data using PCV13 in this population was available.
In September 2014, the ACIP changed its recommendations for adults aged 65 years and older. It is now recommended that these patients receive one dose of PCV13, followed by PPSV23 6 to 12 months later. Patients who have previously received a dose of PPSV23 should receive a dose of PCV13 at 6 to 12 months after PPSV23 administration. The recommendation is a Category 2A recommendation based on the GRADE framework. The new recommendations are based on the currently unpublished final results of the Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA).
The CAPiTA trial was conducted in the Netherlands from 2008-2013 and enrolled approximately 85,000 patients aged 65 years and older. This was a placebo-controlled trial designed to verify the clinical benefit of PCV13 in prevention of pneumococcal pneumonia. The trial found that, compared with placebo, PCV13 demonstrated 45.6% efficacy at prevention of pneumococcal pneumonia due to vaccine-type serotypes. In addition, researchers found that PCV13 had 75% efficacy against vaccine-type IPD.
Unfortunately, since this was a placebo-controlled trial, the results cannot be directly compared with the efficacy of PPSV23. However, in the CAPiTA trial, PCV13 did demonstrate efficacy in preventing pneumococcal pneumonia, something that PPSV23 has not consistently shown. It is also important to remember that CAPiTA was conducted in the Netherlands, and thus results may not be generalizable to conditions elsewhere. The new recommendations note that the evidence for use of PCV13 in adults aged 65 years and older will be reevaluated in 2018 and revised as needed.
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Treanor JJ, Chapter 167: Influenza (including Avian Influenza and Swine Influenza). In: Bennett JE, Dolin R, Blaser MJ. Principles and Practice of Infectious Diseases. 8th ed. Philadelphia; Saunders/Elsevier; 2014.
For more information:
Jeff Brock, PharmD, MBA, is an infectious disease pharmacy specialist at Mercy Medical Center in Des Moines, Iowa. He can be reached at: JBrock@mercydesmoines.org.
Gregory Tallman, PharmD, is a PGY-1 pharmacy practice resident at Mercy Medical Center in Des Moines, Iowa.
Disclosure: Brock and Tallman report no relevant financial disclosures.