NACI Guidance on Influenza Vaccination in Adults 65 and Older

Abstract

Background: Adults 65 years of age and older are at higher risk of influenza complications, such as hospitalization and death. As a result, seasonal influenza immunization is particularly important for this group.

Objective: This supplemental statement provides an evidence summary on the preferential use of one or more of the age-appropriate influenza vaccines for adults 65 years of age and older, over other age-appropriate influenza vaccines.

Methods: The National Advisory Committee on Immunization (NACI)'s Influenza Working Group undertook an overview of existing systematic reviews on the efficacy, effectiveness, safety and cost effectiveness of influenza vaccination in adults 65 years of age and older. Additionally, NACI's evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings and apply an ethics, feasibility and acceptability lens to develop recommendations.

Results: The evidence suggests that high-dose inactivated influenza vaccine (IIV-HD), adjuvanted inactivated influenza vaccine (IIV-Adj) and recombinant influenza vaccine (RIV) offer increased benefits for adults 65 years of age and older when compared to standard dose influenza vaccines. The IIV-HD had the most supporting evidence, followed by IIV-Adj and then RIV. Evidence comparing these enhanced vaccines was limited.

Conclusion: Following a thorough review of the complete body of evidence, NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. NACI also continues to strongly recommend the inclusion of adults 65 years of age and older among those for whom it is particularly important to receive influenza vaccination.

Introduction

Adults 65 years of age and older are at higher risk of severe influenza infection and related complications such as pneumonia, hospitalization and death. This risk is significantly higher with increasing age, presence and severity of chronic medical conditions and higher levels of frailty ^{Footnote 1Footnote 2Footnote 3Footnote 4}. Considering the burden of disease in this population, the National Advisory Committee on Immunization (NACI) has identified adults 65 years of age and older as one of the groups at higher risk of influenza complications for whom influenza immunization is particularly important (Strong NACI Recommendation) ^{Footnote 5}.

NACI has conducted several reviews over the years to evaluate the best available scientific and clinical evidence to develop recommendations for the use of influenza vaccines, with a focus on optimizing influenza protection among older adults in Canada ^{Footnote 6Footnote 7}.

Other than a recommendation for using high-dose inactivated influenza vaccines (IIV-HD) over standard-dose inactivated influenza vaccine (IIV-SD) formulations, NACI has not previously made comparative individual-level recommendations on the use of other available vaccines in this age group. On a public health program level, NACI has recommended that any of the available influenza vaccines authorized in this age group should be used, as there was insufficient evidence on the incremental value of different influenza vaccines to make comparative public health program-level recommendations on the use of available vaccines.

Given the expressed desire by provincial and territorial programs for guidance on optimal product choice(s) for older adults, NACI has undertaken a review of evidence to determine whether any one or more of the age-appropriate influenza vaccines for adults 65 years of age and older should be preferentially used over other age-appropriate influenza vaccines. A systematic review of economic literature was also undertaken to inform public health program decision-making.

Methods

The NACI Influenza Working Group undertook an overview of existing systematic reviews to answer the following research question: Should any age-appropriate influenza vaccine(s) be preferentially used in adults 65 years of age and older? The literature search and data extraction were conducted according to the following population, intervention, comparator and outcomes (PICO) framework (Table 1).

The GRADE-ADOLOPMENT process was employed to adapt recommendations from the United States Advisory Committee on Immunization Practices guideline panel where they assessed the relative benefits and harms of IIV-HD, adjuvanted inactivated influenza vaccines (IIV-Adj) and recombinant influenza vaccine (RIV) compared to one another and with IIV-SD in adults 65 years of age and older ^{Footnote 9Footnote 10}. Evidence synthesis on the efficacy and cost effectiveness of influenza vaccines in adults 65 years of age and older was further expanded with two additional systematic reviews, both developed in collaboration with the Methods and Applications Groups for Indirect Comparisons through the Drug Safety and Effectiveness Network and supervised by the NACI Influenza Working Group. One review examined the efficacy of influenza vaccines in older adults, while the second review delved into the cost effectiveness of seasonal influenza vaccines in older adults. Further details regarding the methodologies employed in both Drug Safety and Effectiveness Network reviews were published in pre-specified protocols ^{Footnote 11Footnote 12}.

To support this work, a systematic assessment of ethics, equity, feasibility and acceptability of influenza vaccine guidance was conducted according to established NACI methods ^{Footnote 13}. The NACI evidence-based process was used to assess the available evidence and develop updated recommendations ^{Footnote 14}. Details and results can be found in the NACI supplemental guidance on influenza vaccination in adults 65 years of age and older ^{Footnote 8}.

Results

NACI's evidence base encompassed an overview of three systematic reviews and meta-analyses to determine if certain authorized age-appropriate influenza vaccines are better suited for adults 65 years of age and older compared to others, analyzing findings from a total of 57 unique primary studies ^{Footnote 10Footnote 15Footnote 16}. Based on the available evidence, NACI concluded that IIV-HD, IIV-Adj and RIV offer greater benefits when compared to IIV-SD, while maintaining the same level of safety (Table 2). Additionally, IIV-HD and IIV-Adj also appear to be cost-effective. Of note, no evidence identified in this review compared mammalian cell culture-based inactivated influenza vaccine (IIV-cc) to other influenza vaccines. Following its thorough review, NACI issued a new recommendation on influenza vaccination in adults 65 years of age and older.

Recommendation

NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. If a preferred product is not available, any of the available age-appropriate influenza vaccine should be used. (Strong NACI Recommendation)

• Where supply of IIV-HD, IIV-Adj or RIV is limited, consideration can be given to prioritizing groups at highest risk of severe outcomes from influenza among adults 65 years of age and older, such as advanced-age older adults (e.g., 75 years of age and older), those with one or more comorbidities, older frail adults and residents of nursing homes and other chronic care facilities.

Summary of evidence

• IIV-HD, IIV-Adj and RIV appear to have increased vaccine efficacy/effectiveness as compared to IIV-SD.
• No definitive conclusion can be reached regarding the superiority of any of these vaccines over one another as there is a limited number of studies directly comparing IIV-HD, IIV-Adj and RIV against each other. Notably, IIV-HD has the most substantial body of supporting evidence, followed by IIV-Adj and then RIV.
• IIV-HD, IIV-Adj and RIV are effective alternatives to IIV-SD, with no identified difference in safety, based on direct evidence among adults 65 years of age and older.
• IIV-HD and IIV-Adj are cost-effective when compared to IIV-SD.

A complete review of evidence and full NACI recommendations are published in the new NACI Supplemental guidance on influenza vaccination in adults 65 years of age and older ^{Footnote 8}. This supplemental guidance aligns with NACI's overarching recommendation for influenza vaccination, available in the NACI Seasonal Influenza Vaccine Statement, which is that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older, noting product-specific contraindications (Strong NACI Recommendation) ^{Footnote 5}.

Conclusion

The available evidence suggests potential advantages associated with IIV-HD, IIV-Adj and RIV compared to IIV-SD; however, the available evidence directly comparing these vaccines to one another is insufficient to establish with certainty that one vaccine consistently outperforms the others. Moreover, data for IIV-HD, IIV-Adj and RIV against IIV-SD demonstrated a comparable safety profile. As the body of evidence exploring whether certain authorized age-appropriate influenza vaccines are better suited for adults 65 years of age and older compared to others continues to grow, NACI will continue to monitor the evolving evidence and will update this guidance as needed. Further evaluation of safety, efficacy and effectiveness data for newer vaccine technologies (e.g., IIV-cc and RIV) as well as vaccine comparisons (pairwise or comparisons between multiple vaccines) between newer influenza vaccines among adults 65 years of age and older are encouraged. Other new and emerging research priorities identified include further evaluation of vaccine efficacy and effectiveness of influenza vaccines stratified by subpopulations of adults 65 years of age and older (e.g., health and frailty status); national-level influenza surveillance data among older adults in Canada; timing of influenza vaccination with respect to duration or waning of protection in adults 65 years of age and older; incorporation and investigation of the impact of community immunity, frailty and longer-term functional outcomes on cost effectiveness; and factors that influence vaccine confidence and acceptability among adults 65 years of age and older in Canada.

Authors' statement

• PDP — Writing–original draft, writing–review & editing
• AS — Writing–review & editing
• JP — Writing–review & editing

The NACI Supplemental guidance on influenza vaccination in adults 65 years of age and older was prepared by P Doyon-Plourde, A Gil, A Sinilaite, W Siu and J Papenburg, on behalf of the NACI Influenza Working Group and was approved by NACI.

Competing interests

JP reports grants and personal fees from Merck, personal fees from AstraZeneca and Enanta and grants from MedImmune, all outside of the submitted work.

Acknowledgements

• NACI Influenza Working Group members: J Papenburg (Chair), M Andrew, P De Wals, I Gemmill, R Harrison, J Langley and A McGeer.
• Former members: D Fell.
• NACI members: S Deek (Chair), R Harrison (Vice-Chair), M Andrew, J Bettinger, N Brousseau, H Decaluwe, P De Wals, E Dubé, V Dubey, K Hildebrand, K Klein, M O'Driscoll, J Papenburg, A Pham-Huy, B Sander and S Wilson.
• Liaison representatives: L Bill (Canadian Indigenous Nurses Association), LM Bucci (Canadian Public Health Association), E Castillo (Society of Obstetricians and Gynaecologists of Canada), J Comeau (Association of Medical Microbiology and Infectious Disease Canada), L Dupuis (Canadian Nurses Association), E Adams (Indigenous Physicians Association of Canada), J Hui (College of Family Physicians of Canada), M Lavoie (Council of Chief Medical Officers of Health), D Moore (Canadian Paediatric Society), M Naus (Canadian Immunization Committee) and A Ung (Canadian Pharmacists Association).
• Ex-officio representatives: V Beswick-Escanlar (National Defence and the Canadian Armed Forces), E Henry (Centre for Immunization and Respiratory Infectious Diseases [CIRID], Public Health Agency of Canada [PHAC]), M Lacroix (Public Health Ethics Consultative Group, PHAC), C Lourenco (Biologic and Radiopharmaceutical Drugs Directorate, Health Canada), S Ogunnaike-Cooke (CIRID, PHAC), K Robinson (Marketed Health Products Directorate, HC), M Routledge (National Microbiology Laboratory, PHAC) and T Wong (First Nations and Inuit Health Branch, Indigenous Services Canada).

The NACI acknowledges and appreciates the contribution of M Hersi, A Howarth, K Gusic, N Moqueet, B Pe Benito, A Stevens, C Tremblay, N Sicard, M Tunis, A Tuite, MW Yeung, K Young, R Yorke and M Xi.

Funding

The work of the National Advisory Committee on Immunization is supported by the Public Health Agency of Canada.