Evaluation of Guillain-Barré Syndrome (GBS) following Respiratory Syncytial Virus (RSV) Vaccination Among Adults 65 Years and Older

Design

Self-controlled case series (SCCS) post-market analysis

N= 3,226,689 doses

Objective

To assess the risk of GBS following RSV vaccinations in adults aged 65 years and older

Study Groups

RSVPreF3+AS01 (AREXVY®; n= 2,202,247)

RSVPreF (ABRYSVO®; n= 1,024,442)

Inclusion Criteria

Medicare Fee-for-Service (FFS) (Parts A, B and D) beneficiaries aged 65 years and older; enrolled on date of first observed RSV vaccination and during 1-year prior to vaccination; incident GBS case during the observation period (i.e., no GBS event in the clean window); vaccinated with either RSVPreF3+AS01 or RSVPreF prior to Jan 28, 2024

Exclusion Criteria

Not disclosed

Methods

Data was collected from Medicare FFS beneficiaries for the incidence of GBS, either during early-season (through April 6, 2024) or end-of-season (through July 13, 2024) vaccination. Patients were observed for 90 days after vaccination, with the incidence of GBS being categorized as within the risk interval (days 1-42) or control interval (days 43-90). GBS was determined inpatient- primary position only, through billing codes (i.e., ICD-10-CM DGN G61.0).

Duration

Study duration: May 2023 to July 2024

Risk interval: 1 to 42 days

Control interval: 43 to 90 days

Outcome Measures

 Incidence of GBS (total); GBS cases during the 90-day observation period; GBS cases after applying clean window restriction; positive predictive value and attributable risk of GBS; incidence rate ratio of GBS

Baseline Characteristics

Early-Season SCCS Analysis

End-of-Season SCCS Analysis

Vaccine

GBS Cases

Total GBS cases**

90-day observation period

After applying clean window restriction

160

105

55

92

74

36

236

119

<70

130

89

<50

*Medicare beneficiaries that received one RSV vaccination and eligible for early- and end-of-season SCCS analysis are presented. Product-specific and total dose counts may not equal due to rounding

** Days per study period: Early season RSVPreF3+AS01= 339; early season RSVPreF3= 311; end of season RSVPreF3+AS01= 437; end of season RSVPreF3= 409

Results

Endpoint

Total GBR medical records

Chart-confirmed GBS case (Level 1,2,3)

Insufficient evidence/not a case (level 4,5)

Records not returned

95

51

24

20

Overall PPV of GBS

Risk interval*

Control interval*

68.0%

62.3%

81.8%

56.8% to 77.5%

48.8% to 74.1%

61.5% to 92.7%

Early vs. end-of-season GBS

RSVPreF3+AS01

RSVPreF3

2.46

2.02

1.19 to 5.08 

0.93 to 4.40

AR per 100,000 doses

RSVPreF3+AS01

RSVPreF3

0.65

0.90

0.18 to 1.12

-0.02 to 1.81

AR Per 100,000 person-years

RSVPreF3+AS01

RSVPreF3

5.71

7.82

1.61 to 9.80

-0.17 to 15.81

*Cases in risk and control intervals are the average number of true cases in the multiple imputation process
Small cell sizes <11; suppressed to protect patient confidentiality

Adverse Events

See Results

Study Author Conclusions

The study suggests an increased risk of GBS following RSV vaccinations, consistent with pre-licensure trials and VAERS data, although the risk is rare. There was no difference in risk with concomitant vaccinations.

InpharmD Researcher Critique

Exploring the "Two-Hit" Phenomenon of Guillain-Barré Syndrome Following Respiratory Syncytial Virus and Influenza Vaccinations

Design

Case presentation

A 2024 case report detailed the clinical presentation, diagnostic approach, and management of Guillain-Barré Syndrome (GBS) in a 60-year-old male who developed progressive neurological symptoms two weeks after receiving simultaneous vaccinations for respiratory syncytial virus (RSV) and influenza. The patient presented initially with subtle symptoms, including lower extremity tingling, metallic taste, back pain, and constipation, which were initially attributed to sciatica and managed conservatively. Over the course of a week, the neurological symptoms progressively worsened, resulting in profound weakness and sensory loss in all extremities and mouth, prompting further evaluation. Diocytologic dissociation, including elevated protein levels (84 mg/dL) with a normal white blood cell count. The neurological assessment demonstrated areflexia and severe motor weakness, with 0/5 strength in the lower extremities and 1/5 strength in the upper extremities, confirming the diagnosis of GBS. Management of the patient's condition involved a five-day course of intravenous immunoglobulin (IVIG) therapy, which stabilized symptoms and prevented respiratory compromise, as evidenced by preserved negative inspiratory force values. Partial clinical improvement was noted at discharge, though residual neurological deficits, including sensory loss and absent reflexes, persisted on follow-up. This case highlighted the temporal relationship between the coadministration of newly approved RSV and influenza vaccines and the onset of GBS, raising concerns about the potential summative risk of vaccine-associated neurological adverse events. Despite the Centers for Disease Control and Prevention (CDC) recommending the coadministration of these vaccines, emerging evidence, including this report, underscores the need for further investigation into the association and the potential benefits of staggered vaccination to mitigate risk. The report also emphasized the importance of prompt recognition and treatment of GBS, as delays in diagnosis and therapy initiation can significantly impact outcomes.

Study Author Conclusions

In this report, we present a case of a 60-year-old man who developed GBS two weeks after simultaneously receiving Pfizer's new RSV vaccine and the influenza vaccine for the first time. GBS significantly impacts a patient's ability to perform tasks in their everyday life, as it did for our patient by affecting his ability to ambulate. In light of this, it is imperative to examine the association with and effects of vaccines and vaccine co-administration with respect to the pathogenesis of GBS. Although the CDC considers the coadministration of these vaccinations to be safe, more studies are needed to further evaluate the incidence of GBS following the coadministration of these vaccinations.