New evidence supports high-dose influenza vaccines

People older than 65 years are at particularly high risk for influenza-related medical complications including hospitalizations and death. In 2009, the FDA approved a trivalent inactivated vaccine with four-times the hemagglutinin antigen per strain, which was thought to improve immune response in seniors.

Background data has largely supported high-dose vaccination among seniors. In a multicenter, randomized controlled trial of high vs standard dose vaccine that included almost 32,000 patients during 2011/12 and 2012/13, 1.4% of high-dose and 1.9% standard-dose patients had an influenza-confirmed influenza-like illness, resulting in a relative efficacy of 24%. Adverse events were slightly, but significantly lower in the high-dose group but 3 high-dose recipients had serious vaccine-related events (which all resolved) vs none in the standard-dose group. A very large Medicare study during 2012/13 and 2013/14 reported similar benefits but only during 2012/13 when H3N2 was more common. Perhaps it is difficult to measure a benefit during more mild, H1N1 seasons? There have been other studies supporting the effectiveness and cost-effectiveness (at least during the 2011/12 and 2012/13 H3N2 seasons) of high-dose vaccine.

One of the larger groups of seniors in the US are patients in the Veterans Health Administration (VHA) system, so it makes sense to measure the benefits of high-dose vaccine using the VHA integrated EMR. In the June 1st JID, authors reported results of a large (industry-funded) retrospective cohort study completed using data from the 2015/16 influenza season (an H1N1 year) that included seniors with at least one inpatient or outpatient visit during the prior year (2014/15). The primary outcome was any hospitalization for pneumonia or influenza. The study used a number of nice methods to adjust for confounding including matching on baseline characteristics and the Care Assessment Need (CAN) score, that is a proxy for frailty. They also adjusted for residual confounding using the prior event rate ratio (PERR) method, which you can read more about here. Basically, PERR adjusts for outcome rates in the baseline period (before vaccination) by dividing the relative rate post-vaccination by the relative rate pre-vaccination (in the baseline period).

The final cohort (before matching) included 104,965 standard-dose and 125,776 high-dose recipients during the 2015/16  influenza season. The matched cohort had 49,091 standard-dose and 24,682  high-dose patients. Using the unmatched and matched cohorts, and using the PERR method with each, the relative vaccine effectiveness of high-dose influenza vaccine was 23% and 25%, respectively. This suggests that high-dose vaccine was effective in preventing influenza or pneumonia-associated hospitalizations among VHA patients.

These results are encouraging since they were from a more mild H1N1 season. Even more encouraging, the authors plan to automate the data extraction process and report vaccine effectiveness within 3 months of the end of each influenza season. But one note of caution, having a high-dose vaccine that is 25% more effective isn't a huge improvement, since influenza vaccines in general aren't very effective. So high-dose influenza vaccine is a small step in the right direction - but more research and new influenza vaccines are needed.