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PRIORITY PRESS -10th Canadian Immunization Conference

Vancouver, BC / December 3-5, 2012

Vancouver - Immunosenescence significantly increases the likelihood of the elderly acquiring serious infections including influenza. If hospitalized, they are at risk for increasing frailty and disabilities. Trivalent inactivated vaccines (TIVs) do help prevent hospitalization in the elderly but sub-optimally. A randomized comparison of 3 seasonal TIVs in subjects ≥65 years of age demonstrated superior antibody responses with an adjuvanted TIV compared with both an intradermal vaccine and a standard TIV. A community-based case control study in a cohort of very elderly patients reaffirmed that the same adjuvanted vaccine provides superior protection against influenza illness compared with both no vaccination as well as standard TIV.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

The impact of hospitalization on frailty and functional outcomes in the elderly should not be underestimated. In data cited by Dr. Janet McElhaney, Professor of Medicine, University of British Columbia, Vancouver, influenza is a disease that targets the elderly in particular. Over 90% of the deaths due to influenza occur in the elderly. For every death due to the infection, “there are 3 to 4 hospitalizations and most of these are occurring in older adults,” Dr. McElhaney noted. Furthermore, once hospitalized, elderly patients are at risk of losing up to 5% of their functional muscle strength for every day they are bedridden.

“With a 10-day hospital admission for a serious influenza illness, they’ve lost half their muscle strength” she added, “and data in general shows that 1 in every 3 older patients admitted to an acute care hospital will be discharged with a higher level of disability and half of them never recover.” Preventing hospitalization from influenza illness in the elderly is therefore very important. Current influenza vaccines are at best moderately effective at keeping older patients out of the hospital due to influenza illness.

Antibody Responses

In the first randomized controlled comparison of 3 seasonal influenza vaccines in seniors, PCIRN investigators evaluated the safety and immunogenicity of an adjuvanted TIV (MF59-TIV or Fluad), an intradermal TIV specifically formulated for seniors (IDV, Intanza 15) and a standard TIV (Agriflu). Approximately 300 subjects were randomized to each of the 3 treatment groups; importantly, participants were non-frail, community-dwelling residents ≥65 years of age who had received the TIV within the previous 2 seasons.

“This was intentional in that it is more representative of the population of Canadian seniors who participate in the annual influenza program, but it does put the vaccines at a disadvantage as it’s harder to demonstrate differences in a substantially immune population,” Dr. David Scheifele, Vaccine Evaluation Center, BC Children’s Hospital, Vancouver, told delegates here. Blood samples were obtained before and 21 to 28 days after vaccination and hemagglutination antibodies (HIA) to each vaccine strain were measured. Baseline antibody titers to both the H3N2 and the H1N1 strains were virtually identical across all 3 arms; uncharacteristically, virtually all patients had immunity to the B strain at baseline so responses to the B component of the vaccine could not be measured.

Based on results from the HIA assay, almost 91% of MF59-TIV recipients achieved seroprotection rates (titers ≥40) to the H1N1 strain compared with 81% of the IDV group and 78% of the TIV group. Approximately 88% of MF59-TIV recipients also achieved seroprotective titers to the H3N2 strain compared with approximately 76% of recipients in both the IDV and the TIV arms. Geometric mean titers (GMT) were also significantly higher to both vaccine strains in the adjuvanted arm compared to the IDV arm and especially to the TIV arm.

“In this age group, you also want to see a fold-rise in mean titers greater than 2,” Dr. Scheifele observed—a response which was achieved with all 3 vaccines, the adjuvanted vaccine having the highest rate of response. Seroconversion rates in excess of 30% (the criteria for this age group) were also achieved with all 3 vaccines for the H1N1 strain.

The adjuvanted and the IDV also met these criteria for the second H3N2 strain. “With the H3N2 strain, the standard trivalent vaccine did not meet these criteria,” Dr. Scheifele observed. At 6 months with 98% follow-up, there were no appreciable differences in the longevity of vaccine responses. “Nevertheless, the rate of potentially protective levels of antibodies was pretty encouraging,” Dr. Scheifele said. Few differences in the adverse event profiles between the 3 vaccines were observed and all were well tolerated.

Vaccine Effectiveness

According to active surveillance data collected by the PCIRN Serious Outcomes Surveillance (SOS) Network during the 2011/2012 influenza season, the seasonal 2011/2012 trivalent inactivated vaccines (TIVs) prevented 45% of hospitalizations from laboratory-confirmed influenza in an overall cohort of 540 cases of hospitalized patients. For those over the age of 65, the seasonal vaccine prevented 52% of hospitalizations from influenza illness (adjusted vaccine effectiveness [VE] rates).

“There was also a demonstrable effect in all age groups including a 41% vaccine efficacy rate in patients over the age of 75,” Dr. Shelly McNeil, Associate Professor of Medicine, QEII Health Sciences Centre, Halifax, Nova Scotia, noted. “Prevention of frailty and maintenance of independence might be important benefits of influenza vaccine that we are not currently targeting,” she suggested.

Ms. Stephanie Konrad, Fraser Health Authority, and colleagues reminded delegates that when the circulating influenza virus does not match vaccine strains well, “the current TIV may be ineffective in the elderly so we need a more effective vaccine to better protect them.”

In a community-based, case-control study, Konrad and colleagues compared the MF59 adjuvanted TIV (ATIV) to the standard TIV in 282 elderly participants, who were tested for influenza (PCR) (84 positive, 198 negative). “Cases were slightly older at a mean age of 85 vs. 82 for controls,” Ms. Konrad noted, “but overall, 47% of our study participants were over the age of 85 and 89% had at least 1 chronic condition.” Approximately 80% had been vaccinated during the 2011/2012 season, 73% of them receiving the ATIV and 27% receiving the TIV. Since half of the influenza cases came from long-term care facilities—“these were very elderly individuals with chronic conditions,” she emphasized.

In multivariate analysis, controlling for age, residency in a long-term care facility, gender and chronic disease, the ATIV vaccine had a 60% efficacy rate against influenza infection compared with no vaccination.

Conversely, regular TIV vaccine did not differ significantly from no vaccination. Among non-long-term care recipients who would more closely resemble the community-dwelling healthy elderly, the ATIV had a statistically significant vaccine efficacy of 73%, whereas the standard TIV had a non-significant vaccine efficacy rate of 42%. “We had a great limitation in this study because it was the quietest influenza season in the past 30 years,” Ms. Konrad observed.

Summary

Prevention of hospitalization from influenza illness is especially important in the elderly as they are particularly vulnerable to poor outcomes. Standard TIVs are moderately effective in this regard. The new adjuvanted MF59-TIV offers superior protection against influenza illness compared with standard TIVs and thus may further reduce the need for hospitalization among the most vulnerable of age groups. 

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