By Marie Rosenthal, MS
In a unanimous vote, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted to expand its recommendation for the use of respiratory syncytial virus vaccines to adults 50 to 59 years of age at increased risk for RSV-associated lower respiratory tract disease (LRTD).
This includes people with conditions such as chronic obstructive pulmonary disease (COPD), asthma, diabetes, cardiovascular disease and those in residential care. This new recommendation applies to both currently approved vaccines—Abrysvo by Pfizer and Arexvy by GSK.
Most adults with RSV hospitalization recorded in the CDC’s RSV Hospitalization Surveillance Network have at least one underlying medical condition, according to Michael Melgar, MD, a medical officer in the CDC’s Coronavirus and Other Respiratory Viruses Division and one of the co-leads of the ACIP work group for RSV in adults.
“Moreover, the types of conditions among adults 50 to 59 are similar to those among adults 60 and older,” he said. “Cardiovascular disease, diabetes and COPD are in the top five for both age groups. Asthma, immune compromise and severe obesity are more common in hospitalized adults 50 to 59 compared with older adults but are still in the top 10 categories in both age groups.”
A Brief RSV Vaccine History
In May 2023, the FDA approved Abrysvo to prevent RSV-LRTD in people 60 years of age and older, and later expanded the indications. The vaccine is indicated to prevent RSV-LRTD in people 60 years of age and older; 18 through 59 years of age who are at increased risk for infection; and during 32 through 36 weeks’ gestational age during pregnancy to prevent RSV-LRTD in infants from birth through 6 months of age.
Arexvy was first approved in May 2023. The FDA approved Arexvy for those 60 and older, and expanded that indication to those 50 to 59 in June 2024.
In June 2024, ACIP recommended these vaccines for all adults ages 75 and older, and for those 60 to 74 who were at increased risk for RSV-LRTD.
According to the CDC, between 15,000 and 20,000 RSV-associated hospitalizations occur annually in U.S. adults aged 50 to 59 years. The risk for hospitalization is highest among those adults with one or more underlying medical conditions such as obesity, cardiovascular disease, diabetes, COPD, asthma, and other chronic or immunocompromising conditions. RSV can exacerbate these conditions and lead to pneumonia, hospitalization or death.
Pfizer’s Abrysvo vaccine is an unadjuvanted, bivalent vaccine that was designed to provide broad protection against RSV-LRTD, regardless of the virus subgroup. In the prefusion state, the RSV fusion protein (F) is a major target of neutralizing antibodies, serving as the basis of Pfizer’s RSV vaccine. Variations in the F protein sequence among RSV-A and RSV-B subgroups are clustered in a key antigenic site, a target for potent neutralizing antibodies.
The GSK vaccine, Arexvy, is an adjuvanted vaccine that contains recombinant RSV glycoprotein F stabilized in the prefusion conformation (RSVPreF3). This antigen is combined with GSK’s proprietary AS01E adjuvant.
ACIP did consider information from a post-marketing observational study that assessed the risk for Guillain-Barré syndrome (GBS) after vaccination with Abrysvo or Arexvy. Based on the FDA’s evaluation of data from clinical trials, reports to the Vaccine Adverse Event Reporting System (VAERS) and the post-marketing study, the FDA had determined that the overall body of evidence suggested an increased risk for GBS with Abrysvo and Arexvy.
The association between vaccination with Abrysvo and Arexvy and GBS was evaluated among Medicare beneficiaries 65 years of age and older. Using Medicare claims data, between May 2023 through July 2024, vaccinations with Abrysvo and Arexvy were identified through CPT/Healthcare Common Procedure Coding System codes and National Drug Codes, and potential cases of hospitalized GBS among recipients of Abrysvo and Arexvy were identified through ICD codes. GBS diagnoses in claims data were confirmed by medical record review when available.
The analyses of all GBS cases based on claims data suggest an increased risk for GBS during the 42 days after vaccination, with an estimated nine excess cases of GBS per 1 million doses of Abrysvo, and an estimated seven excess cases of GBS per 1 million doses of Arexvy administered to individuals 65 years of age and older.
In January, the FDA required and approved safety labeling changes to the prescribing information for Abrysvo and Arexvy based on the totality of data from clinical trials, reports to VAERS and the results of self-controlled case series analyses in an observational study conducted by the FDA that suggest an increased risk for GBS.
While the observational study suggest an increased risk for GBS with Abrysvo and Arexvy, available evidence is insufficient to establish a causal relationship, according to the FDA, and the agency determined that the benefits of vaccination with Abrysvo and Arexvy continue to outweigh their risks.
“Although we could not evaluate inflammatory neurologic events directly in the 50 to 59 population, we know that FDA data support existence of an increased risk of GBS after protein subunit RSV vaccination in Medicare beneficiary 65 and older,” Dr. Melgar said. “Those data had been presented to ACIP at prior meetings. In January, FDA required revision of the prescribing information for the GSK and Pfizer vaccines to include a statement about risk of GBS available. Data suggest that the risk is similar to and potentially greater than that of other currently licensed and recommended adult vaccines.”
This finding only applies to the GSK and Pfizer vaccines, and not the mRNA vaccine being developed by Moderna, he explained.
“However, we should consider the risk of GBS in the context of the public health benefits of RSV vaccination. In June and October last year, ACIP reviewed results of mathematical modeling analysis comparing the numbers of RSV associated outcomes preventable per 1 million persons vaccinated versus the number of potential vaccine attributable cases of GBS. This analysis has been updated to use the most up-to-date information and has been applied to high-risk adults 50 to 59. Importantly, although we made a conservative assumption and applied the attributable GBS risk from Medicare to adults 50 to 59, we should note that the background risk of GBS in a study population can influence the attributable risk estimates and that may be lower in younger adults.”
Jason M. Goldman, MD, FACP, an affiliate professor of general internal medicine at Florida Atlantic University, in Boca Raton, and the liaison representative from the American College of Physicians, said he was glad ACIP lowered the recommendation.
“I have a lot of patients in that 50-plus range with a lot of risk factors, from emphysema to heart disease, lung disease, et cetera, who have wanted this vaccine,” he said. At a suggestion from one panelist that ACIP consider clinical decision-making for this age group, Dr. Goldman said he was opposed to that because fewer people will be vaccinated.
“I really think we should steer away from the shared clinical decision-making, keep the risk factors as broad as possible and allow those patients to get access to the vaccine that the physicians can provide. I really am appreciative of this vote language and think it will be a great service to our patients to be able to expand the indication from 50 plus for those who are at risk,” he added.
The ACIP plans to discuss whether the at-risk recommendation should include adults 18 to 49 years of age at increased risk for RSV in June, according to Dr. Melgar.
The ACIP recommendations will be forwarded to the director of the CDC for review and approval.
