What is the absolute risk reduction of Respiratory Syncytial Virus (RSV) after the RSV vaccine in geriatric patients?

Absolute Risk Reduction of RSV After Vaccination in Geriatric Patients

The absolute risk reduction (ARR) for RSV-associated lower respiratory tract disease in geriatric patients cannot be directly calculated from the available evidence, as the guideline documents report vaccine efficacy (relative risk reduction) rather than ARR; however, based on the reported efficacy rates of 62.9-82.6% and real-world effectiveness of 75.1%, the clinical impact translates to preventing approximately 203,891 hospitalizations per 56.7 million vaccinated adults over 3 years in the US population. 1, 2, 3

Understanding the Efficacy Data

The available evidence primarily reports relative risk reduction (vaccine efficacy) rather than absolute risk reduction:

RSVPreF3 (Arexvy) Efficacy

• 82.6% efficacy against RSV-associated lower respiratory tract disease (LRTD) in the first season 1
• 94.1% efficacy against severe RSV-associated LRTD in the first season 1
• Cumulative efficacy over 3 seasons: 62.9% (97.5% CI: 46.7-74.8%) against RSV-LRTD 1
• 67.4% efficacy (95% CI: 42.4-82.7%) against severe RSV-LRTD over 3 seasons 1

RSVpreF (Abrysvo) Efficacy

• 65.4-88.9% efficacy depending on symptom severity and age group 1
• Efficacy ranges from 57.5% (with ≥2 symptoms) to 81.6% (with ≥3 symptoms) 1

mRNA RSV Vaccine (Moderna mResvia) Efficacy

• 78.7% efficacy (95% CI: 62.8-87.9%) in the first 4 months against RSV-LRTD with ≥2 symptoms 1
• 47.4% efficacy (95% CI: 35.0-57.4%) over all available follow-up time (median 18.8 months) 1

Real-World Effectiveness Data

The most clinically relevant data comes from real-world effectiveness studies:

• 75.1% effectiveness (95% CI: 73.6-76.4%) against RSV-associated acute respiratory infection overall 2
• Vaccine effectiveness was similar across age groups 60-74 years and ≥75 years 1, 2
• Effectiveness ranged from 75% to 82% against RSV-associated hospitalization in adults ≥60 years during the first RSV season 1

Population-Level Impact (Proxy for ARR)

The most tangible way to understand the absolute benefit is through population-level modeling:

For approximately 56.7 million vaccinated adults aged ≥60 years over 3 years, vaccination prevented: 3

• 2,954,465 fewer symptomatic RSV-ARI cases
• 321,019 fewer X-ray confirmed pneumonia cases
• 16,660 fewer RSV-related deaths
• 203,891 fewer hospitalizations
• 164,060 fewer emergency department visits

Calculating Approximate ARR from Population Data

• ARR for hospitalization: 203,891 prevented hospitalizations ÷ 56.7 million vaccinated = 0.36% or 3.6 per 1,000 vaccinated over 3 years 3
• ARR for death: 16,660 prevented deaths ÷ 56.7 million vaccinated = 0.029% or 0.29 per 1,000 vaccinated over 3 years 3

Age-Specific Considerations

Efficacy varies by age group:

Ages 60-69 Years

• 65.4% efficacy against RSV-associated LRTD (RSVPreF3) 1
• 60.3% cumulative efficacy over 3 seasons 1

Ages 70-79 Years

• 74.9% efficacy against RSV-associated LRTD (RSVPreF3) 1
• 70.6% cumulative efficacy over 3 seasons 1

Ages ≥80 Years

• 38.4% efficacy against RSV-associated LRTD (RSVPreF3), though confidence intervals are wide 1
• This lower efficacy in the oldest age group highlights the importance of vaccination before age 80 1

High-Risk Populations

For patients with comorbidities:

• 66.7% efficacy (95% CI: 41.8-82.0%) in participants with ≥1 pre-existing comorbidity 1
• 64.7% cumulative efficacy over 3 seasons in those with comorbidities 1
• Immunocompromised patients showed 67.0-73.1% effectiveness, though stem cell transplant recipients had lower effectiveness (29.4-44.4%) 2

Important Clinical Caveats

Key limitations in interpreting ARR:

• The baseline risk of RSV-LRTD varies significantly by season, geography, and individual risk factors, making a single ARR figure misleading 1, 4
• Community-based studies estimate yearly RSV incidence at 3-7% in adults ≥60 years in high-income countries, but this varies widely 4
• RSV accounts for 6-11% of outpatient respiratory tract infections and 4-11% of adults hospitalized with RTI 4
• Among hospitalized RSV patients, 6-15% require ICU admission and 1-12% die 4

Safety considerations that affect net benefit:

• Excess risk of Guillain-Barré syndrome: 1.8 cases per million doses (RSVPreF3) and 4.4 cases per million doses (RSVpreF) 1
• No excess risk of immune thrombocytopenic purpura was detected in real-world surveillance 2
• The number of RSV-associated hospitalizations, ICU admissions, and deaths prevented per 1 million doses administered exceeded the estimated vaccine-attributable GBS cases across all age and risk groups 1

Clinical Bottom Line

While precise ARR cannot be stated without knowing baseline risk, the clinical impact is substantial: vaccination prevents approximately 3.6 hospitalizations and 0.29 deaths per 1,000 vaccinated adults over 3 years, with higher absolute benefits in those ≥75 years and those with chronic conditions who face higher baseline RSV risk. 3, 1