In July 2023, the Food and Drug Administration (FDA) approved the monoclonal antibody nirsevimab for use in children up to 24 months to prevent severe disease caused by respiratory syncytial virus (RSV).1  In August 2023, the FDA’s Advisory Committee on Immunization Practices (ACIP) published guidelines that recommended all infants younger than 8 months old born in or entering their first RSV season as well as infants and children aged 8 to 19 months at high risk of severe disease entering their second RSV season should receive nirsevimab.1  The ACIP Maternal and Pediatric RSV Work Group pooled efficacy and safety data from 3 studies24  and found that nirsevimab prevented medically attended RSV-associated lower respiratory tract infections by 79.0%, hospitalizations by 80.6%, and ICU admissions by 90.0%.1  Before this, the only FDA-approved drug to prevent severe RSV infection was the monoclonal antibody palivizumab, but it required monthly injections because of its short-term efficacy and was approved only for specific high-risk groups of infants because of its higher cost and lower efficacy.5  The rate of RSV-associated mortality in hospitalized patients in the United States is noted to be less than 1%.6  Likely because of the rarity of death from RSV, no study of this drug has demonstrated mortality benefit, but its effects could be beneficial in decreasing the cost burden of RSV and utilization of health care services. However, widespread nirsevimab rollout has been under way without much discussion around its cost inefficacy, its relatively quickly waning immunity, and the hidden costs that it may pose to pediatric medicine.

To determine cost-effectiveness, Medicaid uses a measure of cost per quality-adjusted life-year (QALY) gained in which QALY is estimated to represent length of life and health-related quality of life as a metric to determine whether a certain health intervention is worth its cost.7  For >30 years, the United States has been using a threshold of $50 000 (or less) per QALY gained to deem a health intervention “cost-effective” and more than $100 000 per QALY gained “cost-ineffective.” The Center for Medicare and Medicaid Services has been barred from using QALY as a metric to determine cost-effectiveness for Medicare coverage decisions, citing that coverage decisions should be based on what is reasonable and necessary, but QALY is still widely used for cost-effectiveness decisions in pediatrics.8  There are at least 9 different health classification systems in pediatrics that can be used to estimate QALY.7  Beyond the obvious challenges of methodology on how to choose and accurately measure attributes that affect quality of life, the QALY in pediatrics is no different than what is used in adults.7  The QALY treats them as equal, but ethically we may question if a life-saving drug is more valuable for the child than for the older adult. The measurement also does not consider risk, or what an individual is willing to pay to avoid a catastrophic risk. The serogroup B meningococcal disease can be absolutely devastating and deadly for a teenager, but the cost per QALY gained for the vaccine ranges from $3.7 to $9.4 million and interestingly, the ACIP does not include it in its routine vaccination schedule.8  Nonetheless, the Centers for Disease Control and Prevention and ACIP used cost per QALY gained to determine whether nirsevimab is cost-effective, and they claimed that it is.1 

Nirsevimab is the only monoclonal antibody included in the Vaccines for Children (VFC) program, a program that allows the Centers for Disease Control and Prevention to use federal funds to purchase vaccines and provide them at no cost to patients who qualify for the program by being either American Indian or Alaska Native, Medicaid-eligible, uninsured, or underinsured.9  The ACIP has the unique legal ability to approve vaccines that will be included in the program.9  All the routine vaccinations with the addition of the COVID-19 vaccine, human papillomavirus vaccine, MenB vaccine, monkeypox vaccine, and now nirsevimab are included in the VFC.9  Qualifications and decisions for why the ACIP approves a vaccine to be included in the VFC are not publicized. However, being part of the government-funded VFC program means increased government spending for widespread nirsevimab prophylaxis on top of private insured costs. The ACIP’s subcommittee Work Group found that for an infant entering their first season of RSV, the base case cost per QALY saved is $102 811,10  using a price of $445 for one injection of nirsevimab (averaged from $495 list price and $395 VFC program price). The model accounted for systemic reactions, injection site reactions, serious adverse events, medical costs, productivity costs, and QALY lost. It also included mortality of infants at increased risk of severe disease as well as savings from palivizumab.10  The Work Group drew its base analysis for QALY from 1 systematic study that was only able to pool together 2 cohort studies focusing on premature infants because the data were so limited.11  The ACIP provided us with more data showing cost and number-needed-to-treat for infants younger than 8 months of age (Table 1).

TABLE 1

Number Needed to Immunize per Event and Cost per Health Event Averted9 

EventNumber of Infants Needed to Immunize to Prevent 1 EventCost per Health Event Averted (at $445/Dose)
Outpatient visit 17 $2662 
Emergency department visit 48 $7473 
Inpatient day 24 $3687 
Inpatient stay 128 $19 909 
ICU day 194 $30 165 
ICU stay 581 $90 464 
EventNumber of Infants Needed to Immunize to Prevent 1 EventCost per Health Event Averted (at $445/Dose)
Outpatient visit 17 $2662 
Emergency department visit 48 $7473 
Inpatient day 24 $3687 
Inpatient stay 128 $19 909 
ICU day 194 $30 165 
ICU stay 581 $90 464 

Infants and children 8 to 19 months with increased risk of severe RSV disease require 2 injections, increasing the cost to $890 per child. The data for this age group are poor, but the best estimate of cost per QALY ranges based on risk from $25 328 to $1 557 544.10  This is the high-risk group that would have received palivizumab, which cost $1661 to $2584 per dose and $361 727 to $1.3 million per QALY.5  But comparison of these 2 drugs may not be valid. Cost efficacy of palivizumab has come under significant scrutiny, and the American Academy of Pediatrics revised their recommendations to only include at-risk infants because of its cost inefficacy.5,12  For some perspective, vaccines deemed cost-effective by the ACIP have costs per QALY ranging from $3000 to 45 000 for the human papillomavirus vaccine in 12-year-old girls, $20 200 for the 13-valent pneumococcal conjugate vaccine in patients <7 years, $980 for the influenza vaccine for adults >65 years, and $31 000 for the recombinant zoster vaccine for immunocompetent adults >50 years.8  To date, the only published statistical model for the United States showed widespread nirsevimab prophylaxis will save $612 million per year, but the static model—funded by the makers of nirsevimab—does not take into account the price tag and expenditures of nirsevimab prophylaxis nor the effects it could have on RSV epidemiologic trends.13 

During the COVID-19 pandemic, we witnessed 2 cohorts of infants being protected from RSV from nonpharmaceutical interventions such as stay-at-home orders, mask mandates, hand hygiene and social distancing, and various other proposed viral epidemiologic theories.14  Analyses in the postpandemic era have shown increased hospitalizations from RSV compared with prepandemic times with increased severity of RSV infections measured by oxygen administration, PICU admission, and length of stay.15  Emerging data have also shown trends of increasing RSV infections in older children.16  These trends are likely explained by waning immunity and immune naivety in the pediatric population rather than more virulent strains.14  The literature has also described palivizumab-resistant RSV strains17  and newly emerging nirsevimab-resistant RSV strains.18 

Because nirsevimab is a monoclonal antibody rather than a vaccine, immunity wanes relatively quickly with an averaged efficacy at 25% after 6 months and 0% after 10 months.10  RSV is ubiquitous in our environment. With nirsevimab given to most infants before 8 months of age, we are only protecting about 1 cohort of infants for 1 RSV season because of its waning immunity. Arguably, we are protecting infants from being infected during their most vulnerable age. But we need to analyze how this will affect infants in their second season of RSV and older children. The pandemic has already given us a glimpse of how protection from RSV for 1 to 2 seasons has affected RSV epidemiologic trends. We saw more infections with more hospitalizations, as well as more severe infections, and trends after the pandemic are still being identified. With the widespread rollout of nirsevimab, we will likely see dramatic decreases in RSV-associated hospitalizations in younger infants, but increased hospitalizations in older infants and children. Although certainly older infants may be less ill from RSV, this increase in older patients may temper the cost-efficacy of the drug in infancy. Although RSV has not yet shown to increase its virulence significantly, with newly emerging nirsevimab-resistant RSV strains, we do not yet know how that will change future RSV strains after widespread prophylaxis.

Widespread rollout of nirsevimab has already begun without much discussion around its cost-effectiveness, waning immunity, or potential downstream effects on older infants, children, and changes in epidemiologic RSV trends. Protecting all infants from RSV infection with a highly effective drug is ground-breaking, but caution should be taken to further investigate how nirsevimab will affect the pediatric population before widespread rollout continues. To do this, further studies need to be completed with dynamic statistical models on nirsevimab’s cost in the United States, investigation into how the pandemic affected RSV trends, and close analysis of how nirsevimab is affecting RSV trends, specifically hospitalization rates and rates of severe infection. A complete understanding of the impact of nirsevimab with a deeper analysis of the consequences of its utilization is needed for governance of this drug.

Dr Neumann conducted background research and data collection, drafted the initial manuscript, reviewed and revised the manuscript, and approved the final manuscript as submitted; and Dr Alverson conceptualized the manuscript, supervised background research and data collection, critically reviewed and revised the manuscript, and approved the final manuscript as submitted.

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Competing Interests

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to disclose.