Article
Supporting Influenza Vaccination in the Older Adult Population in the Community Pharmacy
This article was sponsored by VaxServe, a Sanofi Company.
As healthcare professionals embedded within the community, pharmacists administer vaccines that help provide protection against infectious diseases, such as influenza, through advocating for vaccination.
Pharmacists are well-positioned to recognize the specific immunization needs of adults aged 65 and older and administer the most appropriate influenza vaccine option. The immune system can deteriorate as adults grow older and this population may not respond as well to vaccination.1 Moreover, adults aged 65 and older are at increased risk of developing serious influenza-related complications (eg, hospitalization and death) compared with younger adults.1
Influenza vaccine coverage rates are not ideal in older adults; however, of adults who do receive an influenza vaccination, 39% receive it in a pharmacy.2 Pharmacists have an important opportunity to increase vaccine coverage rates by identifying vaccination opportunities in vulnerable populations, such as when older adults with chronic illnesses visit the pharmacy for prescription pick up.
When choosing among the influenza vaccines, it is important to be aware of options that have proven efficacy and effectiveness to help protect against influenza infection and help prevent influenza-related complications in adults 65 years and older.
RECOMMENDATIONS FROM THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES
On June 22, 2022, the US Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) proposed recommendations that adults aged 65 years and older preferentially receive 1 of the following influenza vaccines: quadrivalent high-dose inactivated influenza vaccine (HD-IIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted inactivated influenza vaccine (allV4). If none of these 3 vaccines are available at an opportunity for vaccine administration, then any other age-appropriate influenza vaccine should be used.3
Notably, there is no preference for any specific vaccine over another because there are limited data from studies or head-to-head, randomized control trials (RCTs) that directly compare the efficacy and effectiveness of the influenza vaccines that can be used to inform specific recommendations.4
Only Sanofi higher-dose flu shots are proven to prevent more flu in older adults than a standard dose influenza vaccine in RCTs.5,6
FLUZONE® HIGH-DOSE QUADRIVALENT (INFLUENZA VACCINE)
Fluzone High-Dose Quadrivalent is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B viruses contained in the vaccine. It is approved for use in persons 65 years of age and older.5 Fluzone High-Dose Quadrivalent provides 4-strain protection against 2 influenza A strains (A[H3N2] and A[H1N1]) and both influenza B lineages (B Victoria lineage and B Yamagata lineage) that unpredictably co circulate each season. It contains 4 times the amount of hemagglutinin (HA) antigen than in a standard-dose influenza vaccine (60 vs 15 micrograms per strain, respectively).5,6
SELECT IMPORTANT SAFETY INFORMATION FOR FLUZONE® HIGH-DOSE QUADRIVALENT (INFLUENZA VACCINE)
Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine.
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
Please see Important Safety Information throughout and at the end of this article. Please see full Prescribing Information for Fluzone High-Dose Quadrivalent.
Clinical evidence
Fluzone® High-Dose (Influenza Vaccine) trivalent formulation is the first and only high-dose influenza vaccine proven to provide superior flu protection in a clinical trial compared with standard-dose Fluzone® (Influenza Vaccine).5 The efficacy of the trivalent formulation is relevant to Fluzone® High-Dose Quadrivalent (Influenza Vaccine) since both vaccines are manufactured according to the same process and have overlapping compositions.5
In a randomized (1:1), controlled trial in adults aged 65 and older (N = 31,803) during the 2011-2012 and 2012-2013 influenza seasons, Fluzone High-Dose (Influenza Vaccine) trivalent formulation provided 24% (95% CI, 10-37) better protection against influenza due to any laboratory-confirmed, circulating strain compared with standard-dose Fluzone (Influenza Vaccine). The prespecified statistical superiority criterion for the primary endpoint (lower limit of the 2-sided 95% CI of the vaccine efficacy of Fluzone High-Dose relative to Fluzone >9.1%) was met.5,6
Safety
In a randomized (2:1), double-blind controlled immunogenicity and safety study in adults 65 and older, solicited injection-site reactions and systemic adverse reactions were slightly more frequent with vaccination with Fluzone High-Dose (Influenza Vaccine) trivalent formulation as compared with standard-dose Fluzone (Influenza Vaccine). The safety analysis set included 2573 Fluzone High-Dose (Influenza Vaccine) trivalent formulation recipients and 1260 standard-dose Fluzone (Influenza Vaccine) recipients. In adults aged 65 and older, the most common injection-site reactions (>10%) were pain and erythema; the most common solicited systemic adverse events were myalgia, headache, and malaise.5,7
Immuno-bridging study
An immuno-bridging study compared the safety and immunogenicity of Fluzone High-Dose Quadrivalent with that of Fluzone High-Dose (trivalent formulation) during the 2017-2018 influenza season. A total of 2670 adults aged 65 years and older were randomized (4:1:1) to receive 1 dose of either Fluzone High-Dose Quadrivalent or 1 of 2 formulations of Fluzone High-Dose containing either influenza B Victoria or B Yamagata lineages.5 Fluzone High-Dose Quadrivalent induced a noninferior immune response compared with 2 Fluzone High-Dose formulations, as assessed by geometric mean antibody titers at day 28 and seroconversion rates, to strains common to formulations of both vaccines, based on pre-specified criteria.5
Fluzone High-Dose Quadrivalent exhibited a similar safety profile compared with Fluzone High-Dose formulations. Rates of any solicited local and systemic reactions, including grade 3 reactions, were similar among Fluzone High-Dose Quadrivalent and Fluzone High-Dose trivalent formulation recipients aged 65 years and older. The most common reactions occurring after Fluzone High-Dose Quadrivalent administration were injection-site pain (41.3%), myalgia (22.7%), headache (14.4%), and malaise (13.2%).5
Real-world evidence
A systematic review and meta-analysis was performed, which included data pooled from 15 published studies conducted in approximately 34 million adults aged 65 years and older over 10 influenza seasons. Identified studies were conducted over the 2009-2010 to 2018-2019 influenza seasons; of which, 7 seasons were A (H3N2) predominant, 3 seasons were A (H1N1) predominant, and 3 seasons were antigenically mismatched.8 HD-IIV3 was more effective than standard-dose influenza vaccine at preventing pneumonia and influenza mortality (39.9%; 95% CI, 18.6-55.6), cardiorespiratory mortality (27.7%; 95% CI, 13.2-32.0), and post-influenza mortality (22.2%; 95% CI, -18.2-48.8).8 Additionally, HD-IIV3 was more effective than standard-dose influenza vaccine at preventing hospital admissions due to influenza illness (11.7%; 95% CI, 7.0-16.1), pneumonia (27.3%; 95% CI, 15.3-37.6), combined pneumonia and influenza (13.4%; 95% CI, 7.3-19.2), and cardiorespiratory events (17.9%; 95% CI, 15.0-20.8).
Select end points are presented in this article; however, influenza-like illness, all-cause hospitalizations, and all-cause mortality were also evaluated in this meta-analysis.8 Study limitations included the following: a high degree of statistical heterogeneity was observed, unmeasured confounders could have affected the results, most outcomes of the reviews were not lab-confirmed and do not necessarily represent strain-specific vaccine effectiveness, and the between studies weighting may have led to overall results that were significant while subanalyses had wider confidence intervals. Study funding was provided by Sanofi Pasteur and the authors were employees of Sanofi Pasteur.8
SELECT IMPORTANT SAFETY INFORMATION FOR FLUZONE® HIGH-DOSE QUADRIVALENT (INFLUENZA VACCINE) (Continued)
If Guillain-Barré syndrome has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone High-Dose Quadrivalent should be based on careful consideration of the potential benefits and risks.
If Fluzone High-Dose Quadrivalent is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be lower than expected.
Please see Important Safety Information throughout and at the end of this article. Please see full Prescribing Information for Fluzone High-Dose Quadrivalent.
FLUBLOK® QUADRIVALENT (INFLUENZA VACCINE)
Flublok Quadrivalent is a vaccine indicated for active immunization against disease caused by influenza A subtype viruses and influenza type B viruses contained in the vaccine. Flublok Quadrivalent is approved for use in persons 18 years of age and older. It contains 3 times the amount of HA antigen than in a standard-dose influenza vaccine (45 vs 15 micrograms, respectively).11
Recombinant technology may provide unique features to an influenza vaccine: it ensures the exact strain matches to World Health Organization and FDA-selected strains; avoids mutations in manufacturing that could lead to reduced vaccine effectiveness; and it may provide cross-protection by providing broader access to antigenic sites, allowing greater accessibility for an immune response.9,10
SELECT IMPORTANT SAFETY INFORMATION FOR FLUBLOK® QUADRIVALENT (INFLUENZA VACCINE)
Flublok Quadrivalent should not be administered to anyone who has had a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
Please see Important Safety Information throughout and at the end of this article. Please see full Prescribing Information for Flublok Quadrivalent.
Clinical evidence
Flublok Quadrivalent is the first and only recombinant influenza vaccine proven to prevent more influenza in adults aged 50 years and older compared with a standard-dose quadrivalent influenza vaccine in a RCT.11,12 In a randomized (1:1), controlled trial that included approximately 9000 adults 50 years and older, Flublok Quadrivalent provided 30% (95% CI, 10-47) better protection against influenza due to any PCR-confirmed circulating strain versus a standard-dose quadrivalent inactivated influenza vaccine, Fluarix Quadrivalent® (Influenza Vaccine).11,12
Safety
The rates of local and systemic adverse reactions were similar (within 7 days of administration) among Flublok Quadrivalent and Fluarix Quadrivalent® recipients.11 For Flublok Quadrivalent, in adults aged 18 through 49, the most common (≥10%) injection-site reactions were tenderness (48%) and pain (37%); the most common (≥10%) solicited systemic adverse reactions were headache (20%), fatigue (17%), myalgia (13%), and arthralgia (10%).11 In adults 50 years of age and older, the most common (≥10%) injection site reactions were tenderness (34%) and pain (19%); the most common (≥10%) solicited systemic adverse reactions were headache (13%) and fatigue (12%).11
Real-world evidence
A retrospective observational cohort study analyzed Medicare fee-for-service claims from 12.7 million adults aged 65 and older who received an influenza vaccination during the 2019-2020 influenza season with 1 of the following vaccines: HD-IIV3 (n = ~7.1 million), egg-based, adjuvanted, standard-dose trivalent (aIIV3) (n = ~2.5 million), egg-based, standard-dose quadrivalent (IIV4) (n = ~1.5 million), cell-cultured standard-dose quadrivalent (cIIV4) (n = ~0.8 million), and RIV4 (n = ~0.6 million). Characteristics during the 2019-2020 season were: influenza A (H1N1) and influenza B (Victoria) were predominating strains with no significant circulation of influenza A (H3N2); an H1N1 strain with an amino acid change emerged late in the season and likely did not substantially affect the vaccine efficacy during the study period; trivalent vaccines contained the influenza B (Victoria) lineage.13
Results of this study showed that RIV4 (Flublok Quadrivalent) was associated with significantly fewer influenza hospital encounters compared with IIV4.13 The relative vaccine effectiveness against influenza hospital encounters with RIV4 (Flublok Quadrivalent) was 13.3% (95% CI, 7.4-18.9); HD-IIV3 (Fluzone® High-Dose trivalent [Influenza Vaccine]) was 6.8% (95% CI, 3.3-10.1), aIIV3 was 8.2% (95% CI, 4.2-12.0); and cIIV4 was 2.8% (95% CI, -2.8 to 8.2).13 These data correspond with 1 of 3 primary analyses. Two additional primary analyses were conducted; these 2 vaccine analyses compared cIIV4 with IIV4 and RIV4 with IIV4.13 Study limitations included the following: lack of access to virological case confirmation may have led to underestimation of the magnitude of differences, residual confounding by unmeasured covariates could have affected the results, and the observation period was cut off at the end of February to avoid potential bias from the overlap between influenza season and the escalation of the COVID-19 pandemic in the United States.13 The authors of this study were affiliated with the FDA and Centers for Medicare and Medicaid Services.
SELECT IMPORTANT SAFETY INFORMATION FOR FLUBLOK® QUADRIVALENT (INFLUENZA VACCINE) (Continued)
If Guillain-Barré syndrome has occurred within 6 weeks following previous influenza vaccination, the decision to give Flublok Quadrivalent should be based on careful consideration of the potential benefits and risks. If Flublok Quadrivalent is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be lower than expected.
Please see Important Safety Information throughout and at the end of this article. Please see full Prescribing Information for Flublok Quadivalent.
ROLE OF THE PHARMACIST
Providing counseling and strong recommendations for influenza vaccines in adults 65 and older is an important clinical priority in the community pharmacy setting. Influenza vaccination in older adults is associated with reduced severity of influenza illness and reduced risk of influenza-associated hospitalization.
Fluzone® High-Dose Quadrivalent (Influenza Vaccine) and Flublok® Quadrivalent (Influenza Vaccine) demonstrated better influenza protection versus a standard-dose influenza vaccine in randomized controlled efficacy trials in older adults.5,6,11,12 Real-world evidence demonstrated better protection against influenza-related complications versus standard-dose influenza vaccines in adults 65 and older.11,13
IMPORTANT SAFETY INFORMATION FOR FLUBLOK® QUADRIVALENT (INFLUENZA VACCINE) AND FLUZONE® HIGH-DOSE QUADRIVALENT (INFLUENZA VACCINE)
Flublok Quadrivalent and Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine (including egg protein for Fluzone High-Dose Quadrivalent). In addition, Fluzone High-Dose Quadrivalent should not be administered to anyone who has had a severe allergic reaction after previous dose of any influenza vaccine.
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
If Guillain-Barré syndrome has occurred within 6 weeks following previous influenza vaccination, the decision to give Flublok Quadrivalent and Fluzone High-Dose Quadrivalent should be based on careful consideration of the potential benefits and risks.
If Flublok Quadrivalent and Fluzone High-Dose Quadrivalent are administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be lower than expected.
Vaccination with Flublok Quadrivalent and Fluzone High-Dose Quadrivalent may not protect all recipients.
For Flublok Quadrivalent, in adults 18 through 49 years of age, the most common injection-site reactions were tenderness and pain; the most common solicited systemic adverse reactions were headache, fatigue, myalgia, and arthralgia. In adults 50 years of age and older, the most common injection-site reactions were tenderness and pain; the most common solicited systemic adverse reactions were headache, and fatigue.
For Fluzone High-Dose Quadrivalent, in adults 65 years of age and older, the most common injection-site reaction was pain; the most common solicited systemic adverse reactions were myalgia, headache, and malaise.
For Flublok Quadrivalent and Fluzone High-Dose Quadrivalent, other adverse reactions may occur.
Please see full Prescribing Information for Flublok Quadrivalent (Influenza Vaccine) and Fluzone High-Dose Quadrivalent (Influenza Vaccine).
REFERENCES
1. CDC. Flu & people 65 years and older. Updated August 26, 2021. Accessed May 20, 2022. https://www.cdc.gov/flu/highrisk/65over.htm
2. Flu Vaccination Coverage, United States, 2020–21 Influenza Season. Published October 7, 2021. Accessed August 10, 2022. https://www.cdc.gov/flu/fluvaxview/coverage-2021estimates.htm
3. Grohskopf LA. Influenza Work Group: summary and proposed recommendations for the 2022-23 influenza season. Advisory Committee on Immunization Practices. Published June 22, 2022. Accessed August 11, 2022. https://www.cdc.gov/vaccines/acip/recommendations.html
4. Grohskopf LA, Alyanak E, Ferdinands JM, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season. MMWR Recomm Rep. 2021;70(5):1-28. Published August 27, 2021. Accessed August 11, 2022. doi:10.15585/mmwr.rr7005a1
5. Fluzone High-Dose Quadrivalent. Prescribing Information. Sanofi Pasteur Inc.
6. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-645. doi:10.1056/NEJMoa1315727
7. Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009;200(2):172-180. doi:10.1086/599790
8. Lee JKH, Lam GKL, Shin T, Samson SI, et al. Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: an updated systematic review and metaanalysis. Vaccine. 2021;39(suppl 1):A24-A35. doi:10.1016/j.vaccine.2020.09.004
9. Arunachalam AB, Post P, Rudin D. Unique features of a recombinant haemagglutinin influenza vaccine that influence vaccine performance. NPJ Vaccines. 2021;6:144. doi:10.1038/s41541-021-00403-7
10. How influenza vaccines are made. CDC website. Updated August 31, 2021. Accessed August 11, 2022. https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm
11. Flublok Quadrivalent. Prescribing Information. Protein Sciences Corporation.
12. Dunkle LM, Izikson R, Patriarca P, et al; PSC12 Study Team. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med. 2017;376(25):2427-2436. doi:10.1056/NEJMoa1608862
13. Izurieta HS, Lu M, Kelman J, et al. Comparative effectiveness of influenza vaccines among US medicare beneficiaries ages 65 years and older during the 2019-2020 season. Clin Infect Dis. 2021;73(11):e4251-e4259. doi:10.1093/cid/ciaa1727
