Centers for Disease Control and Prevention
National Center for Emerging and Zoonotic Infectious Diseases
Post-licensure safety monitoring of respiratory
syncytial virus (RSV) vaccines in adults aged ≥60 years
Tom Shimabukuro, MD, MPH, MBA
On behalf of the Immunization Safety Office, CDC
Advisory Committee on Immunization Practices (ACIP)
February 29, 2024
Topics
▪ Background
▪ CDC vaccine safety monitoring for RSV vaccines in adults aged ≥60 years
• V-safe
• Vaccine Adverse Event Reporting System (VAERS) (co-managed with FDA)
• Vaccine Safety Datalink (VSD)
▪ Summary
2
Background
▪ In May 2023, the U.S. Food and Drug Administration licensed two RSV vaccines
with approvals for use in adults aged ≥60 years
• GSK RSV vaccine (trade name Arexvy)
*
• Pfizer RSV vaccine (trade name Abrysvo)
†
▪ In June 2023, the Advisory Committee on Immunization Practices (ACIP) voted to
recommend that adults aged ≥60 years may receive a single dose of an RSV
vaccine using shared clinical decision-making
‡
*
Package Insert - AREXVY (fda.gov)
†
Package Insert - ABRYSVO (STN 125769/26) (fda.gov); Abrysvo was also authorized on August 21, 2023, for use in pregnant people to prevent lower respiratory tract disease caused by
RSV in infants from birth through six months of age.
‡
Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb
Mortal Wkly Rep. 2023;72(29):793-801.
3
Background, cont.
▪ The most common reactions in prelicensure studies among adults aged ≥60
years receiving RSV vaccine were:
• GSK (Arexvy)
*
RSV vaccine: pain at the injection site (61%), fatigue (34%), and
myalgia (29%)
• Pfizer (Abrysvo)
†
RSV vaccine: fatigue (16%), headache (13%), and pain at the
injection site (11%)
▪ In prelicensure studies
‡
of Pfizer (Abrysvo) RSV vaccine among 20,255 vaccine
recipients aged ≥60 years, 2 cases of Guillain-Barré syndrome (GBS) were
observed within 42 days of vaccination
▪ In prelicensure studies
‡,¶
of GSK (Arexvy) RSV vaccine among 18,304 vaccine
recipients aged ≥60 years, 1 case of GBS was observed within 42 days
of vaccination
*
Package Insert - AREXVY (fda.gov)
†
Package Insert - ABRYSVO (STN 125769/26) (fda.gov)
‡
Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023. MMWR Morb
Mortal Wkly Rep. 2023;72(29):793-801
¶
Gerber S. ACIP presentation slides, October 25, 2023 (1 - GSK RSV - ACIP Core Presentation_CO (cdc.gov))
4
Background, cont.
▪ Clinical trials generally are too small to assess risk for rare adverse events
▪ Due to the small number of GBS cases and size of the prelicensure studies, it is
not known at this time whether these GBS cases or other neuroinflammatory
events occurred due to random chance, or whether RSV vaccination might
increase the risk of these events
▪ Post-licensure safety monitoring
*
of the RSV vaccines is currently ongoing in:
• V-safe
• Vaccine Adverse Reporting System (VAERS)
†
• Vaccine Safety Datalink (VSD)
• Non-CDC systems
*
Vaccine Safety Monitoring | Vaccine Safety | CDC
†
Clinical Immunization Safety Assessment (CISA) Project contributing expertise to VAERS report reviews
5
6
V-safe
New version of V-safe is now available
▪ System requires both previous and
new users to create an account
▪ Includes both email and text
messaging functionality
▪ Vaccines currently monitored:
• RSV vaccines for older adults and
pregnant persons
• COVID-19 vaccines for persons aged 6
months and older
7
V-safe sends health surveys after vaccination
▪ After vaccinations, surveys are sent daily during the first week, then weekly
through 6 weeks
▪ Daily surveys solicit adverse events and health impacts after vaccination
• Local reactions (e.g., pain, redness, swelling)
• Systemic reactions (e.g., fatigue, headache, muscle pain)
• Health impacts (e.g., unable to perform normal daily activities, missed
school or work, or received medical care)
• Additional questions for persons who reported immunocompromise at
vaccination
▪ Weekly surveys solicit new symptoms or conditions after vaccination
▪ Participants reporting medically attended health impacts are
encouraged to complete a VAERS report
8
Characteristic
Vaccine manufacturer (%)
GSK (Arexvy)
N=6,227
Pfizer (Abrysvo)
N=3,746
Manuf
not known
N=5,772
Total
N=15,745
Female sex assigned at birth
59.5 58.0 61.1 59.7
Median age (min, max), years
70 (60, 93) 70 (60, 94) 70 (60, 94) 70 (60, 94)
Ethnicity
Hispanic, Latino, or Spanish
2.7 3.8 3.0 3.1
Race
American Indian or Alaska Native
0.2 0.2 0.3 0.3
Asian
2.9 2.7 2.2 2.6
Black or African American
4.4 7.2 4.6 5.2
Native Hawaiian or Pacific Islander
0.2 0.1 0.1 0.1
White
89.2 85.9 88.7 88.2
Other
0.7 1.2 1.0 1.0
Unknown/prefer not to answer
1.0 1.4 1.5 1.3
Multiracial
1.3 1.2 1.6 1.4
* For 15,745 V-safe participants who enrolled in the RSV 60+ years old protocol and completed ≥1 daily survey during October 20, 2023-January 28, 2024
Demographic characteristics of adults aged ≥60 years
who reported RSV vaccination
*
9
Additional characteristics of adults aged ≥60 years who
reported RSV vaccination
*
Characteristic
Vaccine manufacturer (%)
GSK (Arexvy)
N=6,227
Pfizer (Abrysvo)
N=3,746
Manuf
not known
N=5,772
Total
N=15,745
Immunocompromised
6.8 6.6 6.4 6.6
State of health
Excellent
22.7 22.6 21.5 22.2
Very good
46.9 46.0 46.1 46.4
Good
25.1 25.8 26.5 25.8
Fair
4.9 5.3 5.6 5.3
Poor
0.3 0.2 0.4 0.3
Vaccine(s) co
-administered
24.6 33.8 35.6 30.8
COVID-19
16.0 22.8 23.5 20.4
Influenza
12.6 17.4 20.0 16.5
COVID-19 and influenza
7.3 10.1 11.4 9.5
COVID-19, influenza, and other
0.7 1.1 1.2 1.0
Other
4.9 6.0 5.8 5.5
* For 15,745 V-safe participants who enrolled in the RSV 60+ years old protocol and completed ≥1 daily survey during October 20, 2023-January 28, 2024
10
Reactions and health impacts reported for adults aged ≥60 years at
least once in days 0-7 following RSV vaccination, by manufacturer
*
1.8
0.4
1.3
0.5
1.7
0.3
0
10
20
30
40
50
60
70
80
90
100
Any symptoms Injection site reaction Systemic reaction Unable to complete daily
activities
Unable to work Got medical care
GSK Pfizer Don't know
* For 15,745 V-safe participants who enrolled in the RSV 60+ protocol and completed ≥1 daily survey during October 20, 2023-January 28, 2024
11
Vaccine Adverse Event Reporting System (VAERS)
Strengths
▪ National data
▪ Accepts reports from anyone
▪ Rapidly detects safety signals
▪ Can detect rare adverse events
▪ Data available to public
Limitations
▪ Reporting bias
▪ Inconsistent data quality and completeness
▪ Lack of unvaccinated comparison group
▪ Not designed to assess causality
• VAERS accepts all reports from all reporters without making judgments on causality or judging
clinical seriousness of the event
• As a hypothesis generating system, VAERS identifies potential vaccine safety concerns that can
be studied in more robust data systems
14
VAERS methods
▪ Signs and symptoms of adverse events are coded using Medical Dictionary for
Regulatory Activities (MedDRA)
*
Preferred Terms (PTs)
• MedDRA PTs are not mutually exclusive
• A single report may be assigned more than 1 MedDRA PT
▪ Individual report review of serious
†
reports and medical records, if available
▪ Brighton Collaboration case definitions applied for the neuroinflammatory
conditions, Guillain-Barré syndrome and acute disseminated encephalomyelitis
‡
▪ Reporting rate calculations use doses of vaccine administered for each type of
RSV vaccine
▪ Empirical Bayesian datamining used to detect disproportional reporting for the
entire post marketing period for each product
¶
*
Welcome to MedDRA | MedDRA
†
Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly or birth defect
‡
Sejvar et al. Brighton Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine.
2011;29(3):599-612. Sejvar et al. Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data.
Vaccine. 2007 Aug 1;25(31):5771-92.
¶
DuMouchel W. Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system. Am Statistician 1999;53:177–90.
15
Surveillance of Adverse Events of Special Interest (AESI)
after RSV vaccination
▪ Primary AESIs
• Selected for historical, theoretical, or observed safety concerns (i.e., observed in clinical trials)
• Attempts are made to obtain medical records for all primary AESI reports (serious
*
and non-serious)
• CDC reviews records and abstracts clinically important information
• AESIs may be added to or removed from the list as appropriate
▪ Secondary AESIs
• Monitored via periodic (e.g., weekly) automated data tables
• Can be added to primary AESI list if safety concerns identified
*
Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization,
permanent disability, congenital anomaly or birth defect
16
AESI after RSV vaccination
▪ Outcomes of general interest
• Death
▪ Neurologic/neuroinflammatory conditions
• Guillain-Barré syndrome (GBS), including Miller Fisher variant
• Acute disseminated encephalomyelitis (ADEM)
• Transverse myelitis (TM)
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
▪ Allergic reactions
• Anaphylaxis
▪ Cardiac conditions
• Atrial fibrillation
• Other supraventricular tachycardias (SVT)
▪ Neurologic/neuroinflammatory conditions
• Optic neuritis
• Multiple sclerosis
• Bell’s palsy
• Encephalitis/Encephalomyelitis
• Meningitis/Meningoencephalitis
• Myelitis
▪ Other conditions
• Vaccination errors
• AEs following simultaneous administration with
COVID-19, inactivated influenza, or other adult
vaccines
Primary AESI
Secondary AESI
17
8 participating medical
research centers with
vaccine safety experts
*
More information about clinical consults available at:: Clinical Immunization Safety
Assessment (CISA) Project | CISA | Monitoring | Ensuring Safety | Vaccine Safety | CDC
CISA
Clinical
Immunization
Safety
Assessment
(CISA) Project
▪ clinical consult services
*
▪ clinical expertise for surveillance
▪ clinical research
18
U.S. reports to VAERS following respiratory syncytial virus (RSV)
vaccination among adults ages ≥60 years (as of February 16, 2024)
Vaccine
Doses administered
(as of Feb 2
–3, 2004)
*
Median age
(IQR
†
), years
Female
N (%)
Non
-
serious
N (%)
Serious
‡
N (%)
Total
Reports
GSK (Arexvy)
6,587,912 72 (67–77)
1,674 (67)
2,347 (93) 169 (7) 2,516
Pfizer (
Abrysvo) 3,063,832 73 (68–78) 618 (59) 954 (91) 91 (9) 1,045
Vaccine brand
unknown
Not applicable 73.5 (67-78) 70 (55) 109 (85) 19 (15) 128
Total 9,651,744 72 (67–77)
2,362 (64)
3,410 (92) 279 (8) 3,689
*
Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023, through
February 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims (LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public health clinics and
other settings including workplaces and community locations. These represent projected doses. Based on a sample of retail pharmacies and medical offices of a sample of AMA physicians, IQVIA projects doses
administered in all retail pharmacies and medical offices of all AMA physicians.
†
Interquartile range
‡
Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly or birth defect
19
Most frequently reported MedDRA Preferred Terms
*
among reports to VAERS
following RSV vaccination among adults ages ≥60 years, by manufacturer
(as of February 16, 2024)
Rank
All Reports
(N=3,689)
†,‡
n (%)
Pfizer (Abrysvo)
(N=1,045)
†
n (%)
GSK (Arexvy)
(N=2,516)
†
n (%)
1
Pain in extremity 439 (12) Fatigue 120 (12) Pain in extremity 327 (13)
2
Fatigue 432 (12) Headache 114 (11) Injection site pain 320 (13)
3
Pain 414 (11) Pain in extremity 99 (10) Pain 305 (12)
4
Injection site pain 408 (11) Pain 97 (9) Fatigue 290 (12)
5
Headache 404 (11) Fever 95 (9) Headache 277 (11)
6
Fever 353 (10) Arthralgia 86 (8)
Injection site erythema
267 (11)
7
Injection site erythema 338 (9) Injection site pain 81 (8) Fever 249 (10)
8
Arthralgia 304 (8) Chills 75 (7) Arthralgia 210 (8)
9
Erythema 255 (7) Nausea 71 (7) Erythema 193 (8)
10
Injection site swelling 247 (7) Dizziness 70 (7) Injection site swelling 191 (8)
* Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA Hierarchy | MedDRA)
†
Signs and symptoms are not mutually exclusive
‡
Includes 128 reports with unknown RSV vaccine brand
20
Most frequently reported MedDRA Preferred Terms
*
among reports to VAERS
following RSV vaccination among adults ages ≥60 years (as of February 16, 2024)
Rank MedDRA PT (not mutually exclusive) n (%)
1
Dyspnoea 48 (17)
2
Asthenia 47 (17)
3
Fatigue 38 (14)
4
Gait disturbance 35 (13)
5
Fever 34 (12)
6
Muscular weakness 33 (12)
7
Nausea 31 (11)
8
Guillain-Barré syndrome 30 (11)
9
Intensive care 29 (10)
10
Paraesthesia 29 (10)
Serious
reports
†,‡
(N=279)Non-serious reports
†
(N=3,410)
Rank MedDRA PT (not mutually exclusive) n (%)
1
Pain in extremity 416 (12)
2
Injection site pain 395 (12)
3
Fatigue 394 (12)
4
Pain 388 (11)
5
Headache 384 (11)
6
Injection site erythema 333 (10)
7
Fever 319 (9)
8
Arthralgia 284 (8)
9
Erythema 252 (7)
10
Injection site swelling 245 (7)
* Medical Dictionary for Regulatory Activities Preferred Terms (MedDRA Hierarchy | MedDRA)
†
Includes 128 reports with unknown RSV vaccine brand (109 non-serious and 19 serious)
‡
Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly or birth defect
21
Reports
*
to VAERS of selected AESIs after RSV vaccination among adults
ages ≥60 years (as of February 16, 2024)
Condition
Pfizer
(
Abrysvo
)
GSK
(
Arexvy
)
No brand
name Total
Death 9 22 3 34
Guillain-Barré syndrome (GBS) 18 16 1 35
Acute disseminated
encephalomyelitis (ADEM)
1 0 1 2
Transverse myelitis (TM) 1 2 0 3
Chronic inflammatory demyelinating
polyneuropathy (CIDP)
0 1 0 1
Anaphylaxis 1 1 0 2
Atrial fibrillation 15 38 5 58
Supraventricular tachycardia (SVT) 1 2 0 3
Total 46 82 10 138
▪ On January 19, 2024, a data
mining alert for
disproportional reporting was
detected in FDA Empirical
Bayesian (EB) data mining for
Pfizer (Abrysvo) RSV vaccine
and GBS
▪ No data mining alert for GSK
(Arexvy) RSV vaccine and GBS
has been detected to date
▪ EB data mining is product-
specific and analyzes product-
specific vaccine-adverse event
pairings compared to the
overall VAERS database
*Reports in this table include verified,
unverified, ruled out and duplicate reports
22
Reports to VAERS of Guillain-Barré syndrome (GBS) after respiratory
syncytial virus (RSV) vaccination among adults (as of February 16, 2024)
▪ 23 verified
*
reports of GBS with symptom onset within
42 days (all within 22 days) of RSV vaccination:
• Pfizer (Abrysvo) (n=15), GSK (Arexvy) (n=8)
• Median age: 71 years (IQR: 63,75 years)
• 1 report in a non-pregnant female patient aged 50s
years, received Pfizer (Abyrsvo)
• Median time to onset: 9 days (range 1,22 days
**
)
• 14 males, 9 females
• None were pregnant
• 1 death; patient aged 70s years, male, received GSK (Arexvy)
Preliminary reports
†
of GBS
(N=37)
Under review
‡
(n=6)
Excluded based upon
medical record review
(n=7)
¶
Verified GBS by medical record review (n=23)
*
Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton
Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines
for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.
†
Includes reports identified through automated search and clinical review; all vaccinated Aug 29, 2023, through
Jan 5, 2024
‡
Awaiting medical records
¶
Includes one report in a pregnant person who received Pfizer (Abyrsvo) RSV vaccine; patient did not meet clinical
criteria for Guillain-Barré syndrome following review by independent experts in CISA, including neurologists
** Includes one report after GSK (Arexvy) RSV vaccine with onset at 22 days
Pfizer (Abrysvo)
(n=15)
GSK (Arexvy)
(n=8)
Verified GBS but
excluded due to onset
>42 days (n=1)
23
Reports to VAERS of Guillain-Barré syndrome after respiratory
syncytial virus (RSV) vaccination among adults (as of February 16, 2024)
▪ All 23 verified reports met Brighton Collaboration criteria for GBS
*:
• 3 were Brighton level 1, 12 were Brighton level 2, and 8 were Brighton level 3
• 21 of 23 were also classified as GBS cases (Brighton level 1-3) by at least one CISA neurologist
†
▪ 4 reports involving Pfizer (Abrysvo) RSV vaccine had respiratory symptoms within 4 weeks prior to GBS onset
▪ Other vaccines were given during same visit in 14 of the 23 GBS reports
‡
:
Pfizer (Abrysvo) RSV vaccine n=9
Other vaccine
N
Bivalent mRNA COVID-19 (Pfizer-BioNTech) 3
Bivalent mRNA COVID-19 (Moderna)
13-valent pneumococcal conjugate vaccine
1
aIIV4 (Fluad) 1
Imovax rabies 1
Tdap (Boostrix) 1
Zoster (Shingrix) 1
RIV4 (Flublok) 1
GSK (Arexvy) RSV vaccine n=5
Other vaccine
N
HD-IIV4 (Fluzone high-dose influenza)
Bivalent mRNA COVID-19 (Pfizer-BioNTech)
20-valent pneumococcal conjugate vaccine
1
aIIV4 (Fluad) 1
Covid-19 Moderna 2
Covid-19 Moderna
HD-IIV4 (Fluzone high-dose influenza)
1
* Sejvar et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.
†
One GSK report (death report) (Brighton level 4 per CISA) and 1 Pfizer report aged ≥60 years (Brighton level 4 and 5 per CISA) were not classified as GBS by at least one CISA neurologist after review
‡
Other vaccines were given within 4 weeks of symptom onset and not during same visit in 4 of the 23 reports. 1 Pfizer report, Bivalent mRNA COVID-19 vaccine; 1 GSK report, adjuvanted influenza vaccine;
1 GSK report, unspecified influenza vaccine; 1 GSK report, inactivated influenza vaccine and 20-valent pneumococcal conjugate vaccine
24
Reports to VAERS of other non-GBS neuroinflammatory conditions
after respiratory syncytial virus (RSV) vaccination
*
(as of February 16, 2024)
▪ Transverse myelitis (n=2)
• 1 report each after Pfizer (Abrysvo)
†
and GSK (Arexvy)
‡
▪ Acute Disseminated Encephalomyelitis (n=3)
• 1 report after Pfizer (Abrysvo)
‡
and 2 reports after GSK (Arexvy)
¶
▪ Posterior reversible encephalopathy syndrome (n=1)
• 1 report after Pfizer (Abrysvo)
‡
▪ Acute encephalitis (n=1)
• 1 report after Pfizer (Abrysvo)
†
*
Sejvar et al. Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data.
Vaccine. 2007;25(31):5771-92.
†
Pending medical records
‡
Case classified as listed diagnosis by at least one CISA neurologist
¶
One case classified as insufficient information to verify diagnosis by CISA neurologists; another case pending review of medical records
25
Observed VAERS reports and reporting rates of verified Guillain-Barré
syndrome (GBS) after respiratory syncytial virus (RSV) vaccination
among adults ages ≥60 years
*
Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case
definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.
†
Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023,
through February 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims (LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public
health clinics and other settings including workplaces and community locations. These represent projected doses. Based on a sample of retail pharmacies and medical offices of a sample of AMA physicians,
IQVIA projects doses administered in all retail pharmacies and medical offices of all AMA physicians.
‡
Assumes complete person-time follow-up
¶
Reporting rate for Pfizer (Abrysvo) increases to 4.9 if patient aged 50s years is included
26
Age group
(years)
Risk
window
RSV vaccine
Observed verified
GBS reports
*
(as of Feb 16, 2024)
Doses
administered
†
(as of Feb 2
–
3, 2024)
Observed VAERS
reporting rate
(per million
doses admin)
‡
≥60 21-days
Pfizer (
Abrysvo
)
14
3,063,832
4.6
¶
GSK (Arexvy) 7
6,587,912
1.1
≥60 42-days
Pfizer (
Abrysvo
)
14
3,063,832
4.6
¶
GSK (Arexvy) 8
6,587,912
1.2
Using estimated rate of chart confirmed GBS after mRNA COVID-19 vaccination
in the Vaccine Safety Datalink (VSD) as a proxy for background rate
*
▪ Safety monitoring of mRNA COVID-19 vaccines in the VSD did NOT detect an increased risk of
GBS associated with either of the mRNA COVID-19 vaccines
• Therefore, the rate of GBS following mRNA COVID-19 vaccination can be used as a proxy for the
background rate of GBS in a ‘vaccine-accepting’ population
• This rate is appropriate because it is relatively current and all GBS cases were a priori chart reviewed
• However, there are limitations (e.g., different populations, different time periods, different age groups)
▪ Estimated rate of confirmed cases of GBS in those 65+ years of age following mRNA COVID-19
primary series vaccination in VSD
• 21-day risk interval: 3.4 (95% CI 1.2–7.3) per 100,000 person-years
• 42-day risk interval: 4.5 (95% CI 2.4–7.7) per 100,000 person-years
▪ Expected cases per 1 million RSV doses administered, assuming complete person-time
follow-up
• 21-day risk interval: 2.0 cases per million doses admin (range from 95% CI 0.7–4.2)
• 42-day risk interval: 5.2 cases per million doses admin (range from 95% CI 2.8–8.9)
*
Hanson et al. Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink. JAMA Netw Open. 2022;5(4):e228879 and VSD unpublished data.
27
Observed VAERS reports and reporting rates of verified Guillain-Barré
syndrome (GBS) after respiratory syncytial virus (RSV) vaccination among
adults ages ≥60 years and estimated background rates
Age group
(years)
Risk
window
RSV vaccine
Observed verified
GBS reports*
(as of Feb 16,
2024)
Doses
Admin
(as of Feb 2–
3,
2024)
†
Observed VAERS
Reporting rate
(per million
doses admin)
‡
Estimated
expected rate
(per million
doses admin)
based on VSD
data
¶
≥60 21-days
Pfizer (Abrysvo) 14
3,063,832
4.6
2.0
(95% CI 0.7–4.2)
GSK (Arexvy) 7
6,587,912
1.1
≥60 42-days
Pfizer (Abrysvo) 14
3,063,832
4.6
5.2
(95% CI 2.8–8.9)
GSK (Arexvy) 8
6,587,912
1.2
*
Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton Collaboration GBS Working Group. Guillain-Barré syndrome and Fisher syndrome: case definitions
and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.
†
Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023,
through February 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims (LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public health
clinics and other settings including workplaces and community locations. These represent projected doses. Based on a sample of retail pharmacies and medical offices of a sample of AMA physicians, IQVIA
projects doses administered in all retail pharmacies and medical offices of all AMA physicians.
‡
Assumes complete person-time follow-up
¶
Background data (21-day and 42-day risk windows) on Guillain-Barré syndrome after COVID-19 vaccines from the vaccine safety datalink (cases per million doses); estimate of background rate in a vaccine-
accepting population and used as proxy because data from VSD did not detect an increased risk of GBS after mRNA COVID-19 vaccines (Source: Hanson et al. Incidence of Guillain-Barré syndrome After COVID-
19 Vaccination in the Vaccine Safety Datalink. JAMA Netw Open. 2022;5(4):e228879.) and VSD unpublished data
28
Observed VAERS reports and reporting rates of verified Guillain-Barré syndrome
(GBS) after respiratory syncytial virus (RSV) vaccination among adults ages ≥60
years compared to the VAERS reporting rate for COVID-19 vaccines
Age group
(years)
RSV vaccine
GBS reporting
rate in VAERS
(verified cases)
per million
doses admin
*
≥60
Pfizer (
Abrysvo
)
4.6
≥60 GSK (Arexvy) 1.1
*
Assumes complete person-time follow-up
†
Reporting rate for GBS (21-day risk window) after mRNA Covid-19 vaccines from VAERS in persons aged ≥65 years during December 2020-January 2022. Source: Abara et al. Reports of
Guillain-Barré syndrome After COVID-19 Vaccination in the United States. JAMA Netw Open. 2023;6(2):e2253845.
‡
An association between Ad26 and GBS was observed but not between GBS and mRNA COVID-19 vaccines
21-day risk interval
21-day risk interval
†,‡
29
Vaccine Safety Datalink (VSD)
▪ Established in 1990
▪ Collaborative project
between CDC and 13
integrated healthcare
organizations
▪ Includes electronic health
data annually on ~13.5
million individuals across
all sites which includes ~2.8
million adults aged 60
years or older
30
Observed VSD GBS rates following RSV vaccination in adults
aged ≥60 years through December 30, 2023
▪ The VSD has identified 4 GBS cases within 1-84 days of GSK (Arexvy) RSV vaccination; all 4 cases have
undergone medical record review and have been adjudicated according to Brighton Criteria
*
GSK (Arexvy) Chart Confirmed Results – Brighton Levels 1, 2, or 3
▪ The 4th case, absent from the table above, was classified as Brighton Level 4 and is pending
additional medical record review
▪ Currently no cases of GBS have been observed within 1–42 days after Pfizer (Abrysvo) RSV vaccination
in VSD, but only ~10% of all RSV vaccinations in VSD have been with the Pfizer product
▪ VSD will continue to monitor the safety of RSV vaccines in adults aged ≥60 years and formal sequential
safety analysis will begin in March 2024 using a vaccinated concurrent comparison group (similar to
COVID-19 vaccine safety monitoring)
31
* Sejvar et al. Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599-612.
Vaccine
Risk window
# GBS
cases
# vaccine
doses
Rate per million
doses admin
(95% CI)
Rate per 100,000
person years
(95% CI)
GSK (
Arexvy
)
1-21 days 2 209,653 9.5 (1.2–34.5) 16.6 (2.0–59.9)
GSK (
Arexvy
)
1-42 days 3 209,653 14.3 (3.0–41.8) 12.4 (2.6–36.4)
Summary: Early post-licensure safety monitoring of
RSV vaccines in adults aged ≥60 years
▪ Local and systemic symptoms (e.g., fatigue) were the most commonly reported adverse
events following either of the RSV vaccines
▪ Monitoring in VAERS indicates a higher-than-expected number of GBS reports following
Pfizer (Abrysvo) RSV vaccine, but VAERS is subject to the limitations of passive surveillance
• GBS cases were observed in the pre-licensure clinical trials for both the Pfizer (Abrysvo) and GSK
(Arexvy) RSV vaccines and GBS is included as an adverse event in the labels of both vaccines
▪ Early data from VSD suggest the potential for an increased rate for GBS after GSK (Arexvy)
RSV vaccine, but additional analyses are needed to further assess this potential risk;
insufficient doses of Pfizer (Abrysvo) RSV vaccine used in VSD to inform risk
▪ Monitoring for GBS following RSV vaccines in FDA and CDC (VSD) population-based active
surveillance systems is in progress
▪ CDC and FDA will continue to monitor RSV vaccine safety in VAERS and CDC will continue to
monitor in V-safe
32
Acknowledgements
▪ CDC Immunization Safety Office
• VAERS Team
• V-safe Team
• Clinical Immunization Safety Assessment (CISA) Project
• Vaccine Safety Datalink (VSD)
▪ Food and Drug Administration
• Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation
and Research
▪ National Center for Immunization and Respiratory Diseases
• Coronavirus and Other Respiratory Viruses Division
33
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.
