RSV Vaccines See a Pricey Leap Forward in Disease Prevention

Respiratory syncytial virus (RSV) is a widespread respiratory pathogen causing a range of symptoms, from mild rhinorrhea and cough to severe lower respiratory tract illness (LRTI).^1,2 Subtypes A and B of the virus typically surge during the fall and winter seasons, disproportionately affecting older individuals; young children; and individuals with underlying health conditions, most notably those with asthma and congestive heart failure.³ This leads to approximately 60,000 to 160,000 hospitalizations and 6000 to 10,000 deaths each year.^4,5 RSV is highly contagious due to its ability to spread through respiratory droplets and direct contact, posing a significant public health threat.^6,7

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In May 2023, the FDA approved 2 RSV vaccines, one nonadjuvanted (Abrysvo; Pfizer) and one adjuvanted (Arexvy; GSK), for individuals 60 years and older.^8,9 The nonadjuvanted vaccine was also approved for pregnant individuals from week 32 through week 36 of pregnancy to prevent RSV infection in infants.¹⁰ These vaccines offer hope in mitigating severe RSV infections, though questions about future doses and coordination with other preventive measures persist.

Clinical Studies

Nonadjuvanted, Preservative-Free RSV Vaccine

The nonadjuvanted vaccine was tested in the RENOIR study (NCT05035212), a phase 3, multicenter, randomized, doubleblind, placebo-controlled study that included 34,284 adults 60 years and older.¹¹ The coprimary end points evaluated were vaccine efficacy against RSV-associated LRTI with at least 2 or at least 3 signs or symptoms. The study showed that the nonadjuvanted RSV vaccine was effective in preventing both definitions of RSV-LRTI. Adverse event (AE) rates were similar between groups; AEs mainly consisted of injection site pain.

The nonadjuvanted vaccine was also studied in the Pfizer-funded MATISSE trial (NCT04424316), another phase 3, multicenter, randomized, double-blind, placebo-controlled study that enrolled 14,486 pregnant individuals between 24 and 36 weeks of gestation.¹² The vaccine was shown to be effective against medically attended (defined as an infant being seen by a health care provider) severe RSV-LRTI. Fewer infants in the nonadjuvanted vaccine arm experienced nonsevere RSV-LRTI, but this end point did not meet prespecified success criteria. The nonadjuvanted vaccine AEs were generally mild to moderate, with injection site pain being the most common.

Adjuvanted, Preservative-Free RSV Vaccine

In a global GSK-funded phase 3 trial (NCT04886596), adults 60 years or older were randomized to receive the adjuvanted RSV vaccine or placebo.13 The adjuvanted vaccine demonstrated 82.6% efficacy against confirmed RSV-LRTI over 6.7 months, achieving 94.1% efficacy in severe cases. It was equally effective across RSV A and B subtypes and in patients with coexisting conditions. The adjuvanted vaccine commonly caused mild to moderate injection site pain, fatigue, myalgia, and headache, which typically resolved within days after vaccination.

National Guidelines

The Advisory Committee on Immunization Practices (ACIP) recommends that individuals 60 years and older may opt to receive a single dose of an RSV vaccine through a shared decision-making process with their health care provider, tailored to individual circumstances rather than blanket coverage for a specific age or risk group.^14,15 Additionally, ACIP advises that pregnant individuals receive the nonadjuvanted vaccine between gestation weeks 32 and 36 to protect infants from RSV disease.14 The CDC states that it is safe to administer the influenza, COVID-19, and RSV vaccines during the same health care visit.¹⁶

Pregnancy Considerations

In July 2023, the FDA approved nirsevimab (Beyfortus; Sanofi and AstraZeneca) for prevention of RSV disease in newborns. The CDC does not recommend nirsevimab for most newborns whose birthing parent received the nonadjuvanted vaccine during pregnancy.^9,17

Special Populations

Although the adjuvanted and nonadjuvanted RSV vaccines have not been studied in immunocompromised patients, theoretically they could provide benefits to this high-risk population.^18-20 Both vaccines are inactivated and so are anticipated to be safe for these patients.

Logistical Considerations

The logistical and cost considerations for obtaining the RSV vaccine for adults over 60 years are nuanced due to insurance coverage distinctions.^21,22 Although Medicare Part B covers influenza and COVID-19 vaccines, the RSV vaccine is covered under Part D.²³ The 16 million older adults in the United States without a Part D plan face out-of-pocket costs ranging from $180 to $295 per shot. RSV vaccines for patients aged 60 to 65 years who are not eligible for Medicare should have coverage by private insurance plans because they are recommended by CDC and ACIP, but formulary updates may lag. To avoid surprise costs at the pharmacy, these patients should confirm coverage with their health plan.²⁴ With 2 safe and effective RSV vaccines now available, pharmacists can help providers and patients navigate vaccine access and insurance reimbursement to maximize patient benefit.

References

1. Respiratory syncytial virus infection (RSV). CDC. Updated November 7, 2023. Accessed December 3, 2023. https://www.cdc.gov/rsv/index.html

2. Respiratory syncytial virus (RSV). National Foundation for Infectious Diseases. Updated November 2023. Accessed December 3, 2023. https://www.nfid.org/infectious-disease/rsv/

3. Borchers AT, Chang C, Gershwin ME, Gershwin LJ. Respiratory syncytial virus—a comprehensive review. Clin Rev Allergy Immunol. 2013;45(3):331-379. doi:10.1007/s12016-013-8368-9

4. RSV surveillance & research. CDC. Updated July 17, 2023. Accessed December 3, 2023. https://www.cdc.gov/rsv/research/index.html

5. Griffiths C, Drews SJ, Marchant DJ. Respiratory syncytial virus: infection, detection, and new options for prevention and treatment. Clin Microbiol Rev. 2017;30(1):277-319. doi:10.1128/CMR00010-16

6. Walsh EE, Hall CB. Respiratory syncytial virus (RSV). Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 2015;1948-1960.e3. doi:10.1016/B978-1-4557-4801-3.00160-0

7. Kaler J, Hussain A, Patel K, Hernandez T, Ray S. Respiratory syncytial virus: a comprehensive review of transmission, pathophysiology, and manifestation. Cureus. 2023;15(3):e36342. doi:10.7759/cureus.36342

8. Healthcare providers: RSV vaccination for adults 60 years of age and over. CDC. Updated August 30, 2023. Accessed December 3, 2023. https://www.cdc.gov/vaccines/vpd/rsv/hcp/older-adults.html

9. Healthcare providers: RSV prevention information; RSV immunization for infants and young children. CDC. Updated September 28, 2023. Accessed December 3, 2023. https://www.cdc.gov/vaccines/vpd/rsv/hcp/child.html

10. FDA approves first vaccine for pregnant individuals to prevent RSV in infants. News release. FDA. August 21, 2023. Accessed December 3, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-vaccine-pregnant-individuals-prevent-rsv-infants

11. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med. 2023;388:1465-1477. doi:10.1056/NEJMoa2213836

12. Kampmann B, Madhi SA, Munjal I, et al. Bivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. 2023;388(16):1451-1464. doi:10.1056/NEJMoa2216480

13. Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med. 2023;388:595-608. doi:10.1056/NEJMoa2209604

14. ACIP recommendations. CDC. Updated October 27, 2023. Accessed December 3, 2023. https://www.cdc.gov/vaccines/acip/recommendations.html

15. Rockwell PG. Respiratory syncytial virus vaccination recommendations and other updates from ACIP. Am Fam Physician. 2023;108(4):420-422.

16. What to know about getting flu, COVID-19, and RSV vaccines at the same time. CDC. November 2, 2023. Accessed December 3, 2023. https://www.cdc.gov/respiratory-viruses/whats-new/getting-vaccines-at-same-time.html

17. Jenco M. New VFC program flexibilities may improve access to nirsevimab. American Academy of Pediatrics. 2023. Accessed December 3, 2023. https://publications.aap.org/aapnews/news/26323/New-VFC-program-flexibilities-may-improve-access

18. El Chaer F, Kaul DR, Englund JA, et al. American Society of Transplantation and Cellular Therapy series: #7 - management of respiratory syncytial virus infections in hematopoietic cell transplant recipients. Transplant Cell Ther. 2023;29(12):730-738. doi:10.1016/j.jtct.2023.09.018

19. Cao Y, Zhao D, Xu AT, Shen J, Ran ZH. Effects of immunosuppressants on immune response to vaccine in inflammatory bowel disease. Chin Med J (Engl). 2015;128(6):835-838. doi:10.4103/0366-6999.152683

20. Limited recommendations for adult RSV vaccine dampens demand. U.S. Pharmacist. July 3, 2023. Accessed December 3, 2023. https://www.uspharmacist.com/article/limited-recommendations-for-adult-rsv-vaccine-dampens-demand

21. How to get your flu, COVID-19, and RSV vaccines this year. CDC. October 19, 2023. Accessed December 3, 2023. https://www.cdc.gov/respiratory-viruses/whats-new/how-to-get-your-vaccines.html

22. Wen LS. It shouldn’t be so hard for older adults to receive the RSV vaccine. Washington Post. October 10, 2023. Accessed December 3, 2023. https://www.washingtonpost.com/opinions/2023/10/10/rsv-vaccines-barriers-insurance-coverage-medicare/

23. Does Medicare cover the RSV vaccine? Medicare Interactive. September 11, 2023. Accessed December 3, 2023. https://www.medicareinteractive.org/resources/dear-marci/does-medicare-cover-the-rsv-vaccine

24. Appleby J. Timing and cost of new vaccines vary by virus and health insurance status. KFF Health News. August 24, 2023. Accessed December 3, 2023. https://kffhealthnews.org/news/article/timing-cost-vaccines-insurance-flu-covid-rsv/

About the Authors

Ashlan J. Kunz Coyne, PharmD, MPH, is an assistant professor of clinical and translational research and primary investigator of the Kunz Coyne Laboratory at the University of Kentucky College of Pharmacy in Lexington. Coyne specializes in the pharmacokinetic/pharmacodynamic optimization of antimicrobials against multidrug-resistant bacteria.

Amanda Roy, PharmD, BCIDP, AAHIVP, is an inpatient infectious diseases clinical pharmacist at Zuckerberg San Francisco General Hospital and Trauma Center in California. Roy is passionate about expanding access to and facilitating evidence-based antimicrobial use across the health care system.