Clinical Question

Among older adults, does high-dose influenza vaccine improve protection against influenza compared with the standard-dose version?

Bottom Line

High-dose influenza vaccine provided a 25% relative reduction in the likelihood of developing laboratory-confirmed influenza compared with standard-dose vaccine in patients 65 years and older. This corresponds to a number needed to treat of approximately 220 to prevent a laboratory-confirmed case of influenza, which must be balanced against a slightly higher risk of very rare serious adverse events and higher cost. (Level of Evidence = 1b)

Synopsis

The researchers randomized 31,989 adults, 65 years or older, without acute illness, to receive the standard-dose or a high-dose influenza vaccine over the course of two sequential influenza seasons. The standard dose contained 15 mcg of hemagglutinin per strain, whereas the high-dose version contained 60 mcg. The groups were balanced at baseline. The primary end point was the occurrence of laboratory-confirmed influenza in conjunction with influenza-like illness at least 14 days after vaccination. Patients were instructed to call their study site with any respiratory symptoms, including sneezing, sore throat, cough, rhinorrhea, or difficulty breathing. These symptoms triggered nasopharyngeal swab testing within five days of symptom onset.

In the intention-to-treat analysis, 3,745 high-dose vaccine recipients reported respiratory symptoms prompting symptom review and laboratory testing, whereas 3,827 standard-dose participants experienced the same. Laboratory-confirmed influenza was less likely in those receiving high-dose vaccine (228 vs. 301 [1.4% vs. 1.9%]; relative risk reduction = 24%; 95% confidence interval, 9.7% to 36.5%). The absolute risk reduction was 73 cases, for a number needed to treat of approximately 220. Three high-dose patients had serious adverse events deemed vaccine-related compared with zero standard-dose recipients. However, overall serious adverse events were lower in the high-dose group (relative risk = 0.92; 95% confidence interval, 0.85 to 0.99). The authors caution against extrapolating these results to older adults with moderate or severe acute illnesses because that population was not included in the study. These results may also differ depending on the match of vaccine to the circulating strains of influenza.

Study design: Randomized controlled trial (double-blinded)

Funding source: Industry

Allocation: Concealed

Setting: Population-based

Reference: DiazGranadosCADunningAJKimmelMet alEfficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med2014; 371( 7): 635– 645.