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U.S. Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
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Influenza Updates, Work Group Considerations, and
Proposed Recommendations for the 2024 -25
Influenza Season
Lisa Grohskopf, Jill Ferdinands, and Lenee Blanton
Influenza Division, CDC/NCIRD
June 27, 2024
Jill Ferdinands
Lenee Blanton
Lindsay Trujillo
Joanna Taliano
Andrew Leidner
Rebecca Morgan
Doug Campos- O utcaltAcknowledgements
2
U.S. Influenza vaccine composition for the 2024 -2 5 season
Brief end- of-s eason influenza vaccine safety update
Higher dose and adjuvanted influenza vaccines for solid organ
t
ransplant recipients: Evidence to Recommendations (EtR) Discussion
Proposed recommendations for the 2024 -2 5 seasonOverview
3
Influenza Updates
4
All influenza vaccines marketed in the United States for the 2024- 2 5 season will be
trivalent
There will be no influenza B/Yamagata component, following no confirmed
d
etections of wild -type influenza B/Yamagata viruses since March 2020
U.S. influenza vaccine composition for 2024- 2 5 includes an update to the influenza
A(H3N2) component:
–AnA/V ictoria/4897/2022 (H1N1)pdm09 -like virus for egg -based vaccines
or an A/Wisconsin/67/2022 (H1N1)pdm09 -like virus for cell and recombinant vaccines;
–An A /Thailand/8/2022 (H3N2)- like virus for egg -based vaccines
or an A/Massachusetts/18/2022 (H3N2) -like virus for cell and recombinant vaccines;
–A B/Austria/1359417/2021 (B/Victoria lineage) -l ike virusU.S. Influenza Vaccine Composition for the 2024 -25
Influenza Season
Vaccines and Related Biological Products Advisory Committee March 5, 2024 Meeting Announcement - 03/05/2024 | FDA 5
Immunization Safety Office
Centers for Disease Control and PreventionNATIONAL CENTER FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES
End- of-Season Update: 2023 -2024
Influenza Vaccine Safety Monitoring
•~158 million doses of influenza vaccine distributed in United States*
•Vaccine Adverse Event Reporting System (VAERS) ( co-managed by CDC and
FDA)
-No new safety concerns identified for influenza vaccines
•Vaccine Safety Datalink (VSD) ( collaboration between CDC and 13
integrated healthcare organizations)
-VSD monitors pre -s pecified outcomes using rapid cycle analysis (RCA)**
-~4.8 million doses of influenza vaccine administered in VSD through 5/31/2024
-No new safety concerns identified in influenza vaccine monitoringVaccine Safety Update: 2023 -2024 Influenza Season
12*As of March 9, 2024, Weekly Flu Vaccination Dashboard | FluVaxView | Seasonal Influenza (Flu) |
** Outcomes monitored in VSD for influenza vaccines: acute disseminated encephalomyelitis (ADEM), anaphylaxis (case counts), Bell's palsy,
encephalitis, Guillain- Barré syndrome, seizures, and transverse myelitis; Li et al. Post licensure surveillance of influenza vaccines in the Vaccine
Safety Datalink in the 2013– 2014 and 2014– 2015 seasons (wiley.com) Pharmacoepidemiol Drug Saf. 2016 Aug;25(8):928- 34. •.
Higher Dose and Adjuvanted Influenza Vaccines
for Solid Organ Transplant Recipients: EtR Discussion
Background
8
Solid Organ Transplantation in the United States
National Data, Organ Transplant and Procurement Network (OPTN). National data - OPTN (hrsa.gov)
U.S. Organ Transplants Performed, 2023
All 46,632 (100)
By age group N (%)
<18 years 1,916 (4)
18-64 years 33,610 (72)
≥65 years 11,104 (24)
Organ(s) N (%)
Kidney 27,332 (59)
Liver 10,660 (23)
Heart 4,545 (10)
Lung 3,026 (6)
Kidney/pancreas 812 (2)
Pancreas 102 (0.2)
Heart/lung 54 (0.1)
05000100001500020000250003000035000400004500050000
2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022Total Solid Organ Transplants Performed
in the U.S. By Year, 2000- 2023
Transplants, n
9
Per ACIP recommendations, SOT recipients should receive an age-ap propriate
inactivated or recombinant influenza vaccine (i.e., an IIV or RIV)
–Live attenuated influenza vaccine (LAIV) is not recommended for immunocompromised populations
Immunosuppressive regimens might contribute to diminished response to vaccines
High- d ose (HD -IIV) and adjuvanted (aIIV) inactivated influenza vaccines have been
studied in SOT recipients
American Society for Transplantation (AST) states that high- d ose or boosted dosing
might be preferable post -transplant
HD-I IV and aIIV are approved for ages ≥65 years, and might not be covered by
insurance when administered to persons under age 65 yearsRecommendations for Influenza Vaccination of SOT
Recipients
ACIP , Prevention and Control of Seasonal Influenza with Vaccines, 2023 -24. https://www.cdc.gov/mmwr/volumes/72/rr/rr7202a1.htm
Danziger -Isakov L et al, Clin Transplant 2019;33(9):e1356310
Should high- do se inactivated, adjuvanted inactivated, and/or
recombinant influenza vaccines be recommended as an option for
influenza vaccination of solid organ transplant recipients who are younger than the approved age indication?
–<65 years for high -d ose and adjuvanted influenza vaccines
–<18 years for recombinant influenza vaccine
Policy Question
11
Public Health Importance
EtR Domain 1
12
The number of transplants performed
ea
ch year, and post -transplant survival
have increased
Approximately 430,000 recipients a
live in 2020
–0.1% of U.S. populationPublic Health Importance —Scope of Population
Median recipient survival (years)
Organ 1987 -2012 1987 -2021
Kidney 12.4 14.8
Liver 11.6 14.6
Heart 9.5 11.7
Lung 5.2 5.6
Pancreas 13.3 16.1
Recipients alive, n
Organ June 2015 June 2020
Kidney 200,000 255,738
Liver 74,945 98,842
Heart 29,172 37,419
Lung 12,100 17,500
Pancreas 14,161 19,458
*Considering recipients of the most commonly transplanted organs,
for whom systemic immunosuppression is generally required
Organ Transplant and Procurement Network (OPTN). National data - OPTN (hrsa.gov)
Rana et al, JAMA Surgery 2015; 150(3):252 -259
Ferreira et al, Digestive Diseases and Sciences 2023;68:3810 -3817 OPTN/SRTR 2015 Annual Data Report
OPTN/SRTR 2020 Annual Data Report 2020 ADR (hrsa.gov) 13
SOT recipients require lifelong immunosuppressive medications.
Manifestations of influenza can be more severe
–Lower respiratory tract disease, including pneumonia, occurs in 22 -49% of SOT
recipients
In a 5 -year cohort of SOT recipients with influenza (n=477):
•21% had lower respiratory tract disease on presentation
•69% were hospitalized
•11% admitted to an intensive care unit
• 8% required mechanical ventilation
•
3% died (all- c auses) within 30 days
Public Health Importance —Disease Burden
14Mombelli et al, Exp Rev Anti- infect Ther 2020;18:103 -112
Kumar et al, Cin Infect Dis 2018;67:1322 -1329
Is influenza among solid organ transplant recipients a problem of public health
importance?
No
Probably no
Probably yes
Yes
Varies
Don’t know
WG Judgement: Public Health Importance
1515
Benefits and Harms
EtR Domain 2
16
Population, Intervention, Comparator, and Outcomes
Population Solid organ transplant recipients aged ≥6 months
Interventions High -dose (HD -IIV), MF59 -djuvanted (aIIV), or recombinant (RIV) trivalent or quadrivalent influenza
vaccines
Comparator Single intramuscular dose of trivalent or quadrivalent unadjuvanted standard dose influenza vaccines
Outcomes Primary outcomes
Benefits:
•Medically-attended influenza (Critical)
•Influenza -associated hospitalization (Critical)
•Laboratory-confirmed influenza —immunogenicity data acceptable (Important)
Harms:
•Transplant rejection or graft failure (Critical)
•Neuroinflammatory conditions , e.g. GBS, ADEM (Critical)
•Other immune -related adverse events, including new onset or exacerbation of an autoimmune
condition (Critical)
17
9 papers describing 9 studies:
– 8 randomized; 1 cohort
Vaccines and comparisons:
–HD- IIV3 vs. SD -IIV3 2
–Double-dose vs. single-dose SD-IIV3 2
–aIIV3 vs. SD - IIV3 3
–aIIV3 vs. HD - IIV3 vs. SD -IIV4 1
–aIIV3 (most participants, no comparator) 1
–No papers examining RIV
Transplant populations:
–Kidney 4
–Heart 1
–Mixed 4 (40 -80% kidney)No papers reported on medically -
a
ttended influenza, neuroinflammatory
conditions, or immune -mediated adverse
events (all critical outcomes)
Only one pediatric study (omitted from
m
eta-analysis/GRADE)
Cohort study excluded from GRADE g
iven small size, lack of a comparison
group, and availability of randomized studies
7 papers included in GRADEStudy Characteristics (n=9)
18
Summary—Benefits: aIIV3 vs SD- IIV
19Outcome N studies
(n participants)Pooled RR (95% CI) GRADE Certainty Importance
Influenza- associated hospitalization 1 (403) 2.90 (0.12, 70.71) Low Critical
Medically -attended influenza 0 - - Critical
Lab- confirmed influenza 1 (403) 0.97 (0.43, 2.18) Moderate Important
Seroconversion to H1N1 3 (558) 1.37 (1.09, 1.72) Low Important
Seroconversion to H3N2 3 (558) 1.51 (1.25, 1.82) Low Important
Seroconversion to B 3 (558) 1.64 (1.28, 2.11) Low Important
Seroprotection to H1N1 3 (558) 1.06 (0.98, 1.14) Very low Important
Seroprotection to H3N2 3 (558) 1.20 (1.07, 1.33) Low Important
Seroprotection to B 3 (558) 1.17 (1.01, 1.34) Low Important
Summary—Benefits: HD- IIV3 vs SD- IIV
20Outcome N studies
(n participants)Pooled RR (95% CI) GRADE Certainty Importance
Influenza- associated hospitalization 1 (393) 3.05 (0.12, 74.32) Low Critical
Medically -attended influenza 0 - - Critical
Lab- confirmed influenza 2 (565) 1.09 (0.52, 2.27) Moderate Important
Seroconversion to H1N1 2 (554) 2.46 (1.86, 3.27) Moderate Important
Seroconversion to H3N2 2 (554) 1.67 (1.38, 2.02) Moderate Important
Seroconversion to B 2 (554) 1.90 (1.46, 2.46) Moderate Important
Seroprotection to H1N1 2 (554) 1.03 (0.95, 1.11) Low Important
Seroprotection to H3N2 2 (554) 1.13 (1.01, 1.26) Moderate Important
Seroprotection to B 2 (554) 1.22 (1.08, 1.38) Moderate Important
Summary—Harms
21Outcome Studies (N) Pooled RR (95% CI) GRADE Certainty Importance
aIIV3 vs SD-IIV
Graft rejection 3 (517) 0.28 (0.06, 1.34) Moderate Critical
Neuroinflammatory events 0 - - Critical
Other autoimmune events 0 - - Critical
HD-IIV3 vs SD-IIV
Graft rejection 3 (579) 1.00 (0.32, 3.06) Moderate Critical
Neuroinflammatory events 0 - - Critical
Other autoimmune events 0 - - Critical
Summary of Evidence: aIIV3 vs SD -IIV
Outcome Importance No. studies Included in profile Favored vaccine Certainty
Benefits
Medically -attended influenza Critical 0 - - -
Influenza- associated hospitalization Critical 1 Yes Neither Low
Laboratory -confirmed influenza Important 1 Yes Neither Moderate
Immunogenicity (surrogate outcome)
Seroconversion to A(H1N1) Important 3 Yes aIIV3 Low
Seroconversion to A(H3N2) Important 3 Yes aIIV3 Low
Seroconversion to B Important 3 Yes aIIV3 Low
Seroprotection to A(H1N1) Important 3 Yes Neither Very Low
Seroprotection to A(H3N2) Important 3 Yes aIIV3 Low
Seroprotection to B Important 3 Yes aIIV3 Low
HarmsTransplant rejection/graft failure Critical 3 Yes Neither Moderate
Neuroinflammatory conditions Critical 0 - - -
Other immune -mediated adverse events Critical 0 - - -
22
Summary of Evidence: HD -IIV3 vs SD- IIV
Outcome Importance No. studies Included in profile Favored vaccine Certainty
Benefits
Medically -attended influenza Critical 0 - -
Influenza- associated hospitalization Critical 1 Yes Neither Low
Laboratory -confirmed influenza Important 2 Yes Neither Moderate
Immunogenicity (surrogate outcome)
Seroconversion to A(H1N1) Important 3 Yes HD-IIV3 Moderate
Seroconversion to A(H3N2) Important 3 Yes HD-IIV3 Moderate
Seroconversion to B Important 3 Yes HD-IIV3 Moderate
Seroprotection to A(H1N1) Important 3 Yes Neither Low
Seroprotection to A(H3N2) Important 3 Yes HD-IIV3 Moderate
Seroprotection to B Important 3 Yes HD-IIV3 Moderate
HarmsTransplant rejection/graft failure Critical 3 Yes Neither Moderate
Neuroinflammatory conditions Critical 0 - -
Other immune -mediated adverse events Critical 0 - -
23
Few studies; most are small (4 of 7 have <100 participants)
No direct evidence of relative benefit or either HD -i iv3 or aIIV3 vs SD -IIV
–Only indirect evidence (immunogenicity)
Variability in timing of immunogenicity endpoints and how they are
rep
orted
No information for critical outcomes of medically -a ttended influenza,
neuroinflammatory conditions, or other immune- mediated events
–Given study sizes, power probably not adequate
No evaluations of RIV
Limitations
24
How substantial are the desirable anticipated effects?
Minimal
Small
Moderate
Large
Varies
Do
n’t know
WG Judgement: Benefits and Harms
25
How substantial are the undesirable anticipated effects?
Minimal
Small
Moderate
Large
Varies
Don’t know
WG Judgement: Benefits and Harms
26
Do desirable effects outweigh undesirable effects?
Favors intervention
Favors comparison
Favors both
Favors neither
Varies
Don’t know
WG Judgement: Benefits and Harms
27
Benefits of the intervention
No studies found
Very low
Low
Moderate
High
Harms of the intervention No studies found
Very low
Low
Moderate
HighBenefits and Harms: Certainty of Evidence
28What is the overall certainty of the evidence for the critical outcomes?
Values and Preferences
EtR Domain 3
29
No direct evidence was identified reflecting values or preferences for specific influenza
vac
cine types among SOT recipients
There might be a healthcare provider preference for HD -II V, evidenced by the
recommendations of the American Society for Transplantation and various transplant programs
Values and Preferences for Influenza Vaccine Types
Danziger -Isakov L et al, Clin Transplant 2019;33(9):e13563
COVID -19 and Flu Vaccination Information for Transplant Patients - Penn Medicine30
Does the target population feel that the desirable effects are large relative to undesirable
effects?
No
Probably no
Probably yes
Yes
Varies
Don’t know
WG Judgement: Values
31
Is there important uncertainty about or variability in how much people value the main
outcomes?
Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
WG Judgement: Values
32
Acceptability
EtR Domain 4
33
Acceptability of a recommendation for high- d ose vaccine is possibly
evidenced by recommendations of the AST and some transplant
programs for high- dose vaccine
Acceptability might be limited among healthcare and public health
s
ystems and insurers by need for changes in standing orders,
immunization information systems, and electronic medical record platforms
Acceptability Considerations
34
Is the intervention acceptable to key stakeholders?
No
Probably no
Probably yes
Yes
Varies
Don’t know
WG Judgement: Acceptability
35
Resource Use
EtR Domain 5
36
No economic analysis was conducted:
–Population ~430,000 as of 2020
–Insufficient data concerning relative effectiveness of influenza vaccines in SOT populations
–Insufficient data indicating extent to which use of these vaccines is already occurring among off -l abel
age group SOT recipients
HD-I IV3 and aIIV3 more costly ($73- 77) than unadjuvanted influenza vaccines ($21 -34)
Is the Intervention a Reasonable and Efficient Allocation of
Resources?
Influenza Vaccine Pricing (2023 -24), CMS.gov ( https://www.cms.gov/medicare/payment/part -b-drugs/vaccine -pricing )37
Is the intervention a reasonable and efficient allocation of resources?
No
Probably no
Probably yes
Yes
Varies
Don’t know
WG Judgement: Resource Use
38
Equity
EtR Domain 6
39
No literature was found concerning use of enhanced influenza vaccines
a
mong transplant recipients
Among Medicare beneficiaries aged ≥65 years in a single- se ason (2015 -16),
Black, Asian, and Hispanic persons were 26% to 32% less likely to receive HD-IIV3 than White persons
A WG member noted other potential barriers for SOT recipients:
–SOT recipients face barriers to receiving newer influenza vaccines as they are usually
e
xcluded from clinical trials, and there are few data for this population
–Transplant programs with greater financial resources might be able to purchase va
ccines for their patients, whereas those less well- resourced might notEquity
Mahmud et al, Lancet Healthy Longevity 2021;2:e143 -e153
40
What would be the impact on health equity?
ReducedProbably reducedProbably no impactProbably increasedIncreased
Varies
Don’t know
WG Judgement: Equity
41
Feasibility
EtR Domain 7
42
Factors favoring feasibility
The recommendation might improve
a
ccess, if more likely to be covered by
insurance.
If covered, insurance and r
eimbursement concerns should be
minimal.
Vaccination should be easily im
plementable in office and retail
settings that serve adults.
The vaccines are licensed and r
outinely stocked.
Factors not favoring feasibility
A recommendation stating that vaccines
a
re acceptable options (as opposed to a
preferential recommendation) might not compel insurers to cover them.
Use of vaccine in a new age group might r
equire changes in standing orders,
Electronic Medical Record programming, and immunization information systems.Feasibility
43
Is the intervention feasible to implement?
No
Probably no
Probably yes
Yes
Varies
Don’t know
WG Judgement: Balance of Consequences
44
Balance of Consequences and
Sufficiency of Information
45
Undesirable consequences c learly outweigh desirable consequences in most settings
Undesirable consequences pr obably outweigh desirable consequences in most settings
The balance between desirable and undesirable consequences i s closely balanced or uncertain
Desirable consequences pr obably outweigh undesirable consequences in most settings
Desirable consequences c learly outweigh undesirable consequences in most settings
There is insufficient evidence to determine the balance of consequences
WG Judgement: Balance of Consequences
46
Is there sufficient evidence to move forward with a recommendation
Yes
No
WG Judgement: Sufficiency of Information
47
Proposed Recommendations
48
Routine annual influenza vaccination is recommended for all persons aged
≥
6 months without contraindications.
–Same as previously
All persons should receive an age- a ppropriate influenza vaccine (i.e., one
approved for their age), with the following exception: solid organ transplant recipients aged 18 through 64 years on immunosuppressive medication regimens may receive either HD -IIV3 or aIIV3 as an
acceptable option (without a preference over other age- appropriate IIV3s
or RIV3). Proposed Recommendations for Influenza Vaccination,
2024 -25 (For Vote)
49
For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY: 1 -888 -232-6348 www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation
use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.
50