Real-World Insights: Nirsevimab’s Protection Against RSV in Infants

Each year in the U.S., respiratory syncytial virus, commonly known as RSV, leads to approximately 58,000 to 80,000 hospitalizations among children under age 5. The virus is particularly harmful to infants, especially those under 6 months, and can obstruct their breathing, often resulting in bronchiolitis or pneumonia. Because RSV infects most children in their first year of life, the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) in August 2023 recommended that infants 8 months and younger be given a single dose of the long-acting monoclonal antibody nirsevimab.

While safe and effective, real-world data on its effectiveness against RSV-associated emergency department encounters and hospitalizations among U.S. infants were limited. To expand the data, Elizabeth Rowley, DrPH, a Principal Statistical Associate, and Steph Battan-Wraith, PhD, a Senior Research Associate, both from Westat’s Clinical Research group, conducted a study of the 2023 to 2024 respiratory virus season. Here they discuss their challenges, methodology, and findings.

Q. What public health or clinical challenges motivated this study?

A. Elizabeth Rowley: The ACIP was deeply concerned about the high number of hospitalizations among infants due to RSV infections. After advising that nirsevimab be given to infants 8 months and younger, ACIP wanted real-world evidence proving its effectiveness against RSV-associated emergency department visits and hospitalizations among this population. Our research would provide data to ACIP indicating how well this product worked, inform future immunization policy decisions, and increase immunization confidence.

Q. What research method did you use?

A. Steph Battan-Wraith: We conducted a test-negative analysis using electronic health record (EHR) data from 6 healthcare systems, including emergency department encounters and hospitalizations with a diagnosis of RSV-like illness (RLI) from October 8, 2023, to March 31, 2024. We estimated the antibody’s effectiveness by comparing children who received nirsevimab with those who didn’t among RSV-positive and RSV-negative encounters, adjusting for a range of demographic categories, calendar day, and geographic region, and excluding infants whose mother received RSV vaccination during pregnancy. This research was supported by the CDC VISION Network, a multisite collaboration that gathers medical, laboratory, and vaccination records to inform public health strategies.

Q. What were the biggest challenges in designing and conducting this large, multisite analysis?

A. Steph Battan-Wraith: Nirsevimab was a brand-new product, introduced at different dates across the health system sites, so we didn’t have consistency in that area. Plus, there were supply issues early on during the 2023-24 RSV season. Short supply meant clinical decisions about which infants would receive the antibody had to be made, and this varied from site to site. We were already faced with sample size challenges given the very narrow age group of interest, and the staggered and slow rollout of the new product exacerbated this issue.

Elizabeth Rowley: To compare infants who received nirsevimab to those without any RSV protection, we also needed to know the mother’s RSV vaccination status. So, we worked closely with our VISION Network collaborators at each site, who gave careful consideration to how this linkage could be accomplished. The VISION Network is very large, collecting data from roughly half a million hospitalizations and emergency department visits during the 2023-24 respiratory virus season. What our collaborators found is that this linkage was possible for many, but not all, babies. Once we limited our analysis to babies who could be linked and were in the correct age window, our analysis included approximately 10,000 hospitalizations and emergency department visits. An analysis like this would not have been possible in a smaller network.

Q. In what ways does this study demonstrate the strengths of using real-world evidence to assess product effectiveness?

A. Steph Battan-Wraith: Clinical trials are highly regulated and aren’t as representative of the general pediatric population. Real-world evidence demonstrates how this product actually functions within the broader U.S. and highlights the value of this immunization when applied outside of the rigorously monitored clinical trial setting.

Q. What were your findings?

A. Elizabeth Rowley: Our findings are published in The Lancet Regional Health – Americas. To summarize, nirsevimab showed a high degree of effectiveness. In fact, it was 77% effective against RSV-associated emergency department encounters and 98% against RSV-associated hospitalizations.

Q. Given the product’s effectiveness in preventing hospitalizations, what does that mean for hospitals, pediatricians, and public health agencies?

A. Steph Battan-Wraith: The burden on hospitals will be greatly reduced. The fact that if infants received a single dose of nirsevimab, 98% fewer infants would require hospitalization should be welcome news to pediatricians, hospitals, public health agencies, and parents. We hope providers will recommend nirsevimab, demand that insurers cover it, and work to increase parental awareness about it.

Q. What are the next steps for RSV prevention research, especially as the protection from a single dose of nirsevimab may wane over time?

A. Elizabeth Rowley: We don’t know how durable nirsevimab’s protection is, so we want to continue to monitor it. In the fall, we will collaborate with the CDC to evaluate the effectiveness of a second new antibody immunization product with the support of the VISION Network. But the bottom line is that it’s important for parents to know this immunization product’s immense value.