RSV vaccine - a primary care update on serious risks and benefits

Old data, plus real world stuff

This fall marks the second year that we’ve had Respiratory Syncytial Virus (RSV) vaccines to offer older adults. Chances are you have received one, are eligible to receive one, or have older family/friends who qualify but are wondering what to do. I’ve been fielding lots of questions about the RSV vaccines from patients over the past several weeks… and this year we have more evidence-based answers than last year. I apologize in advance for a percentages-heavy post here… but I thought this topic deserved to be properly examined. This is new stuff, and I have a healthy fear of Guillain-Barré syndrome. You’ll see what I mean.

Bullet points

• People over age 75 should get an RSV shot if they haven’t had one already (CDC).

• People aged 60-74 with health conditions like heart or lung diseases, complicated diabetes, weakened immune systems, or who live in long-term care also qualify (CDC). Here is the complete list of health conditions that increase risk and favor vaccination in this age group.

• No recommendation was made for at-risk people aged 50 to 59, as the ACIP panel stated they had too little data at this point upon which to base a guideline.

• There are three options: Arexvy and Abrysvo are in their second years of availability, and there is a newcomer from Moderna called mResvia.

• mResvia, which uses an mRNA platform, was approved in May 2024 - a bit too late to get into many pharmacies for this fall. We have less real world evidence and experience with this newest one.

• If I had a choice I would slightly prefer Arexvy brand from GSK over Abrysvo brand from Pfizer. Although there has been no head-to-head study, post-approval surveillance detected a possible, slight risk of Guillain-Barré syndrome (GBS) with Abrysvo more than Arexvy.

  (Guillain-Barré syndrome is a rare autoimmune disorder in which the body's immune system attacks peripheral nerves, causing rapid-onset muscle weakness and sometimes paralysis. More below.)

• There were no reports of Guillain-Barré syndrome among people in the clinical trials that led to the approval of mResvia

• Anecdotally, my older patients who received a shot (Arexvy or Abrysvo) all did well last year.

• RSV vaccine for pregnant mothers, and the RSV monoclonal antibody injections for infants are beyond the scope of this post. See chart below for a quick reference and I’ve hyperlinked it for more information.

• In terms of the seasonal respiratory viruses: Covid is still my top concern, followed by influenza, and then RSV.

• RSV rates in the U.S. are still low as of today, but are just starting to rise in the Southeast. If you’re going to get the shot, by the end of this month seems prudent.

• According to U.S. estimates, around 24% of adults over age 60 got the shot last year, including more than 30% of adults aged 70 or over. Demand is down so far this year, partly because of the narrowed age groups recommended, no need for a second shot yet, and many early adopters are already vaccinated.

  

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Highlights from my RSV vaccine post last year

Last year physicians were told to have a “shared decision making” session with our patients. This was a big ask for many, as the shots were pretty new and the details nuanced. I did my best with this deep dive post, and here are a couple evergreen ideas from that post that still inform the present:

Respiratory Syncytial Virus in adults typically presents with a cough, sore throat, congestion, runny nose, headache, mild fevers, and fatigue. It’s one of 200+ pathogens that can cause what we think of as a “bad cold.” RSV can sometimes progress to pneumonia, bronchitis, and other lower respiratory infections. Babies, the elderly, adults with certain chronic diseases (listed here), weakened immune systems, and those living in nursing homes or long-term care facilities are at higher risk for severe disease.

I had one 68 year old patient hospitalized with RSV pneumonia last year, unvaccinated. Most RSV cases are undiagnosed as rapid testing is mostly done through emergency rooms. I can only test for influenza, Covid, and strep in the office. FYI I saw a patient this week for a 30 minute review of his diabetes, hypertension, arthritis, and mental health. At the end of the visit he disclosed headache, sore throat, cough, and “a head cold.” I tested him and it came back as influenza B. I was masked like usual, and he’s going to be fine, though he spread his virus unmasked for the past week at work, etc. Getting my flu shot soon, though the crystal ball predicts it’s not a great match this year, though better than nothing.

Back to RSV.

For adults over the age of 65, RSV season in the U.S. results in about 100,000-160,000 hospitalizations, and 6,000-10,000 deaths. That’s out of a population of about 56 million. In terms of the impact on adults in this age group, RSV runs a close second to influenza in terms of severity. When we talk about “hospitalization” always think about how miserable someone feels to end up at the hospital, and how potentially serious their condition is to be hospitalized. There are a lot of people who suffer at home, too, but are short of hospitalization.

The original studies that landed FDA approval for the first two RSV vaccines showed:

For the Pfizer RSV vaccine called Abrysvo, studied in 34,000 patients:

• 90% effective against severe lower respiratory infections like pneumonia and bronchitis caused by RSV

• Protection remained high at 79% through the second year after the shot

• 67% effective against RSV infection of any severity, including mild illness

For the GSK RSV vaccine called Arexvy, studied in 25,000 patients:

• 94% effective against severe lower respiratory infections like pneumonia and bronchitis caused by RSV, and 82% effective at preventing less severe cases

• 70% effective against RSV infection of any severity, including mild illness

• And broken down by season: overall efficacy of 82% against lower respiratory tract disease during the first season, 77% for mid-season, and 67% over two seasons. Against severe disease, efficacy was 94.1% during the first season, 84% at mid-season, and 79% over two seasons.

Unfortunately these vaccines were not studied in enough high risk patients and elderly patients over 75-80 years of age to perform a subgroup analysis. For example, the average age of the patients in the Pfizer study was 68. Last year I wrote: We will have to see this year if the vaccines do particularly well for the >80 y.o. population, and hopefully without higher adverse events.*

*And now we have more data here in 2024. See below.

Finally, a quick note about GBS. The background rate of GBS in the general population is 1-3 cases per 100,000 people each year. Based on the Abrysvo clinical trial we were potentially seeing 3 cases in just 20,000 people in the Pfizer study. That equates to 15 cases/100,000. Was this seen in the real world last season?

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CDC bottom lines from last year’s RSV season

In the real world, here’s how the new vaccines did last year:

Arexvy:

• 77% effective in preventing RSV-associated emergency department encounters

• 83% effective in preventing RSV-associated hospitalizations in adults 60 and older

• 1.8 reports of GBS per 1 million doses administered

Abrysvo:

• 79% effective in preventing RSV-associated emergency department encounters

• 73% effective in preventing RSV-associated hospitalizations in adults 60 and older

• 4.4 reports of GBS per 1 million doses administered

Although GBS reports were reassuringly low, the methods used to gather these numbers were based on voluntary reporting through the Vaccine Adverse Event Reporting System (VAERS), and may underestimate true rates.

The expected rate with shots — i.e. the rate at which GBS occurs among people who get vaccinated with other vaccines that are not known to seriously elevate one’s risk of developing GBS — is 2.0 extra cases per 1 million doses in the 21 days after a vaccination.

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The new vaccine, mResvia, only has phase 2/3 randomized, blinded placebo-controlled clinical trial data. It worked well, yet seemed less durable as time went on:

• Efficacy of a single dose of mResvia against symptomatic RSV was approximately 80% during the first 4 months following vaccination.

• This protection from symptomatic disease dropped to 56% during the first 12 months after vaccination. Compare this to Arexvy, which was 68% effective over 23 months, and Abrysvo which was still 78% effective after 16 months.

• Protection against severe disease/hospitalization? The trial was too small to assess this.

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RSV vaccines worked well last year to reduce hospitalizations

Another study just published in JAMA last month found that RSV vaccination in adults aged 60 and over was highly effective, reducing the risk of RSV-associated hospitalization by 75% during the 2023-2024 season, on par with other studies. This effectiveness remained consistent across different age groups, with similar risk reductions observed for adults aged 60-74 (75% reduction) and those 75 and older (76% reduction). The findings expand on previous trial data by demonstrating protection against hospitalization in a population that more closely represents those at high risk of severe RSV disease, including older adults and immunocompromised individuals. This is what we wanted to see after the initial trials were too small for this subgroup analysis.

Approximately 10% of 3,000 participants contracted confirmed RSV.

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Year three after vaccination?

Hot off the press this week. GSK's phase 3 trial data for their RSV vaccine Arexvy shows continued protection across three seasons in adults 60 and older, with cumulative efficacy of 62.9% against lower respiratory tract disease (like pneumonia, bronchitis) and 67.9% against severe disease compared to placebo.

In the actual third year after vaccination, the vaccine demonstrated 48% efficacy against RSV-related lower respiratory tract disease, suggesting sustained risk reduction even as protection may wane over time.​​​​​​​​​​​​​​​​ I’m guessing boosters will be recommended for the highest risk folks by 5 years out.

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Here are two new studies that highlight which populations are at most risk of severe RSV disease, and how severe disease with hospitalization is associated with cardiac events like heart failure.

Older adults in assisted-living are at highest risk of RSV hospitalization

This is a really important consideration for families who have older members in assisted living.

A study in Journal of Infectious Disease prospectively analyzed hospitalizations in a single New York county during 2017 to 2020 and calculated rates of severe RSV:

• Among community-dwelling older adults, rates of infection requiring hospitalization were:

  • 91 per 100,000 (for ages 65–74)

  • 191 per 100,000 (for ages ≥85)

• These rates were dwarfed by rates among older adults (age, ≥65) in facilities:

  • 738 per 100,000 for those in assisted living

  • 439 per 100,000 for those in skilled nursing facilities

• The authors ascribe the especially high rates among assisted-living residents to their ongoing contact with the wider community (visitors, staff, and fellow residents in closer contact). These are the folks who REALLY should get the RSV vaccines, by the numbers at least.

25% of people hospitalized with RSV also experienced CV events

This cross-sectional study published in JAMA Internal Medicine analyzed data from 6,248 hospitalized adults aged 50 or older with RSV infection over five RSV seasons, finding that 22.4% experienced acute cardiac events, most commonly acute heart failure.

Patients with underlying cardiovascular disease had a higher risk of acute cardiac events, and those who experienced such events had a greater risk of ICU admission and in-hospital death. The study provides important baseline data on cardiac complications of RSV infection in older adults prior to the availability of RSV vaccines.

Prevent hospitalization with vaccines as above, prevent the chance for RSV to cause collateral heart events.

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One more mention of Guillain-Barré syndrome

(GBS) is a rare autoimmune disease that occurs when the body's immune system attacks the peripheral nerves. As described above, it seems like there is a very slight risk of this condition after Abrysvo, and maybe Arexvy. The absolute risk of GBS might be as low as 5 cases per million doses as reported by VAERS, or 15 cases per 100,000 if the rate in the initial small randomized controlled trial holds up in the real world. We don’t know this number with certainty, but it’s not a big number at least.

• Symptoms of GBS may include tingling and weakness in the legs, which can spread to the arms and upper body. Other symptoms include muscle pain, numbness, difficulty swallowing or breathing, and vision problems. 

• Causes: often preceded by a bacterial or viral infection, but the exact cause is unknown. Other possible causes include illnesses, traumas, or vaccines. 

• Treatment: plasma exchange, immunoglobulin therapy, physical therapy, and supportive care. 

• Outlook: most people recover fully from GBS, but some experience permanent nerve damage. Recovery can take weeks or years. 

• Risk factors: GBS can affect people of all ages, but it's more common in adults and men. 

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Take home

In conclusion, the landscape of RSV vaccination for older adults has evolved significantly since 2023, with clearer recommendations and more robust evidence supporting its effectiveness.

The CDC now recommends RSV vaccination for all adults over 75 and those 60-74 with specific health conditions, offering three vaccine options: Arexvy, Abrysvo, and mResvia.

Real-world data has demonstrated the vaccines' high efficacy in preventing RSV-related hospitalizations and emergency department visits, particularly benefiting those at highest risk, such as residents in assisted living facilities. And while protection wanes, there is no need for a booster as of now for those who already received their RSV shot last year.

The vaccines also have the implied potential of reducing secondary complications like cardiac events associated with RSV hospitalizations.

While there are slight differences between the vaccines, including a possible rare risk of Guillain-Barré syndrome (specifically with Abrysvo?), overall they represent a significant advancement in protecting older adults from severe RSV illness. Those older adults in my family got their shots last year.

I think the CDC guidelines are good, and I emphasize the shots for the over 75 group, and 60-75 with those listed health issues. I give extra credit to people who pronounce “syncytial” correctly, or who can describe what a “syncytium” is!

[ Noun: a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei. ]

Take good care.

I think you’ll agree there is no way to explain all this during an office visit.

I hope this helps!