Making strides to help protect our most vulnerable this flu season

When making vaccine decisions with their patients, healthcare providers (HCPs) rely on treatment guidance from the Centers for Disease Control and Prevention (CDC). They trust the agency to review the science behind vaccines to help drive informed decisions.

The CDC’s Advisory Committee on Immunization Practices (ACIP) recently granted preferential recommendation for influenza vaccines for adults 65+, including Fluzone^® High-Dose Quadrivalent [Influenza Vaccine], a quadrivalent high-dose flu vaccine, and Flublok^® Quadrivalent [Influenza Vaccine], a quadrivalent recombinant flu vaccine. If none of the vaccines preferentially recommended are available at the time of administration, then any other age-appropriate influenza vaccine should be used¹

Further, the CDC published this recommendation in its Morbidity and Mortality Weekly Report (MMWR), a public health journal highlighting the latest updates from the field, including reports and recommendations derived from science-based research.² For the full ACIP recommendation please refer to the August 26 MMWR.

Publication of this updated guidance is a step forward in ensuring HCPs have the information and resources they need to help protect their patients from the flu and its severe complications. The wide-spread adoption of this new recommendation will help raise awareness of the importance of new guidelines for vaccinating older populations who are at higher risk for severe flu-related complications.

Flublok Quadrivalent and Fluzone High-Dose Quadrivalent are vaccines indicated for active immunization against disease caused by influenza A subtype viruses and type B viruses contained in the vaccine. Flublok Quadrivalent is approved for use in persons 18 years of age and older. Fluzone High-Dose Quadrivalent is approved for use in persons 65 years of age and older.^3,4

Select 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.^3,4

Please see Full Important Safety Information below.

However, more can be done to help provide HCPs with clearer guidance on best practices for vaccinating older adults against the flu. Understanding the differences between all of the vaccine options and their potential benefits and risks is incredibly important in making informed decisions with older patients. The ACIP recommendation and subsequent MMWR publication reaffirm that not all vaccines are the same when it comes to helping to protect older populations.²

About Fluzone High-Dose Quadrivalent (Influenza Vaccine)

In a randomized controlled efficacy trial of approximately 32,000 adults aged 65+, Fluzone High-Dose (Influenza Vaccine) trivalent formulation provided 24% (95% CI: 10-37) better protection against influenza due to any lab confirmed circulating strains vs a standard dose Fluzone (Influenza Vaccine) during the 2011-2012 and 2012-2013 flu seasons.⁴ 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 Compared to Fluzone (Influenza Vaccine), the most common side effects for Fluzone High-Dose (Influenza Vaccine) were slightly more frequent and included injection site pain, muscle aches, headache and fatigue. In a randomized controlled trial (4:1:1) conducted in the 2017-2018 season between Fluzone High-Dose Quadrivalent and two formulations Fluzone High-Dose (the trivalent formulation), in 2670 patients aged 65+, Fluzone High-Dose Quadrivalent was proven at least as immunogenic as Fluzone High-Dose for geometric mean titers (GMTs) and seroconversion rates for all 4 influenza strains. Fluzone High-Dose Quadrivalent exhibited similar safety profile to Fluzone High-Dose. 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%).⁴

In a meta-analysis of approximately 34 million adults aged 65+ included in 15 published studies, Fluzone High-Dose (Influenza Vaccine) demonstrated 10 years of real-world evidence in preventing more influenza complications than standard dose vaccines. Fluzone High-Dose (Influenza Vaccine) was more effective at preventing flu and pneumonia hospitalizations (13.4%; 95% CI, 7.3-19.2), flu and pneumonia death (39.9%; 95% CI, 18.6-55.6) and pneumonia hospitalizations (27.3%, 95% CI, 15.3-37) versus standard dose vaccines. Fluzone High-Dose (Influenza Vaccine) point estimates shown higher vaccine effectiveness at preventing flu-related hospitalizations (11.7%; 95% CI,7.0-16.1), post-influenza deaths (22.2%; 95% CI -18.6-48.8) and preventing cardiorespiratory hospitalization (17.9%; CI 15.0-20.8) and cardiorespiratory mortality (27.7%; 95% CI, 13.2-32.0) versus standard dose vaccines.⁶

This study was conducted over 10 influenza seasons between the 2009-2010 season and 2018 2019 influenza seasons. Results show seven seasons were A (H3N2) predominant, three seasons were A (H1N1) predominant and three seasons were antigenically mismatched. Study limitations include ⁶:

• High degree of statistical heterogeneity observed.
• Unmeasured confounders could affect the results.
• Most outcomes of the reviews were not lab confirmed and do not necessarily represent strain specific vaccine effectiveness.
• The between studies weighting may lead to overall results that are statistically significant while sub analyses have wider confidence intervals.

Study funding was provided by Sanofi Pasteur and the authors were employees of Sanofi Pasteur.⁶

About Flublok Quadrivalent (Influenza Vaccine)

Sanofi’s Flublok Quadrivalent (Influenza Vaccine) is the first and only recombinant influenza vaccine for adults age 18+ that was proven to be more effective than a standard-dose influenza vaccine at preventing flu in people age 50+ in a randomized controlled trial (RCT).³

In a RCT that included approximately 9,000 adults age 50+, Flublok Quadrivalent (Influenza Vaccine) provided 30% (95% CI: 10-47) better protection against influenza due to any PCR-confirmed circulating strain versus a standard dose of Fluarix Quadrivalent (Influenza Vaccine). In this relative efficacy and safety trial of adults age 50+, the rates of local and systemic adverse reactions were similar among both groups, and 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%).³

In a retrospective observational cohort study of 12.7 million adults aged 65+ during the 2019-2020 flu season, Flublok Quadrivalent (Influenza Vaccine) was associated with significantly fewer influenza hospital encounters compared with standard-dose influenza vaccines. Within the adjusted analysis, Flublok Quadrivalent (Relative Vaccine Effectiveness (RVE), 13.3%; 95% CI, 7.4-18.9%), an egg-based adjuvanted trivalent flu vaccine (RVE, 8.2%; 95% CI, 4.2-12.0%), and an egg-based high-dose trivalent flu vaccine (RVE, 6.8%; 95% CI, 3.3-10.1%) were significantly more effective in preventing hospital encounters than the reference egg-based standard dose quadrivalent vaccine, while a cell-cultured standard dose flu was not significantly more effective than an egg-based standard dose quadrivalent flu vaccine (RVE, 2.8%; 95% CI, -2.8%, 8.2%).⁷

The data presented represent one of three primary analyses. Two additional primary analyses were conducted: two vaccine analyses comparing a cell-based quadrivalent flu vaccine with an egg-based standard-dose quadrivalent, and Flublok Quadrivalent (Influenza Vaccine) with an egg-based standard dose quadrivalent flu vaccine.⁷

During the 2019-2020 flu season, 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.⁷

These findings are specific to the 2019-2020 flu season and the Study Limitations include⁷:

• 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 results.
• 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 U.S.

Study funding was provided by the U.S. FDA and Centers for Medicare and Medicaid Services.⁷

Sanofi continues to be a global leader in flu vaccines. We never settle and remain committed to help ensure at-risk populations have access to scientifically backed vaccine options. By making clinically-driven and data-informed recommendations, the healthcare community can help protect all appropriate people — regardless of race, ethnicity or socioeconomic status.

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 the Prescribing Information for Flublok Quadrivalent. Please see the Prescribing Information and Patient Information for Fluzone High-Dose Quadrivalent.

References

1. Centers for Disease Control and Prevention. Summary: ‘Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP)—United States, 2022-23’: Adults Aged ≥65 Years. Available at: https://www.cdc.gov/flu/professionals/acip/summary/summary-recommendations.htm#65years Accessed September 2022.
2. Grohskopf LA, Blanton LH, Ferdinands JM, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022–23 Influenza Season. MMWR Recomm Rep 2022;71(No. RR-1):1–28. DOI: http://dx.doi.org/10.15585/mmwr.rr7101a1
3.Flublok Quadrivalent [Prescribing Information]. Protein Sciences Corporation.
4.Fluzone High-Dose Quadrivalent [Prescribing Information]. Sanofi Pasteur Inc.
5. 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.
6. Lee JKH, Lam GKL, Shin T, Samson SI, Greenberg DP, Chit A. Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: An updated systematic review and meta-analysis. Vaccine. 2021;39 Suppl 1:A24-A35.
7. 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.

The content in the above article is intended for US healthcare professionals only.

MAT-US-2204923-v1.0-10/2022