This economic evaluation investigates the real-world cost-effectiveness of nirsevimab immunization in preventing respiratory syncytial virus (RSV)–related pediatric hospitalizations.
Key Points
Question
What is the real-world cost-effectiveness of nirsevimab immunization in preventing respiratory syncytial virus (RSV)–related pediatric hospitalizations?
Findings
In this multicenter economic evaluation including 5924 RSV-related hospitalizations in 19 pediatric hospitals in Italy, nirsevimab immunization was effective and cost saving in most centers, resulting in negative incremental costs. In 2 centers with later campaign initiation limited to newborns, immunization was less cost-effective with higher costs relative to hospitalizations prevented.
Meaning
These findings suggest that nirsevimab was a cost-saving RSV prevention strategy, highlighting the importance of timely, broad implementation.
Abstract
Importance
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children, imposing a substantial burden on health care systems. Nirsevimab, a long-acting monoclonal antibody, has shown high efficacy in clinical trials, and modeling studies suggest it may be cost-effective; however, real-world evidence on its cost-effectiveness in European health care settings remains limited.
Objective
To evaluate the real-world cost-effectiveness of nirsevimab immunization in preventing pediatric hospitalizations due to RSV.
Design, Setting, and Participants
This multicenter, observational, real-world cost-effectiveness analysis was conducted between October 1, 2022, and March 31, 2025. Precampaign data were modeled using Poisson regression models to estimate expected hospitalizations in the absence of immunization. Data were gathered from 19 pediatric hospitals distributed across 11 Italian regions, from northern to southern areas. Included were all pediatric hospitalizations with RSV-specific International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnoses recorded at participating hospitals between October 1, 2022, and March 31, 2025.
Exposures
Regional nirsevimab immunization campaigns with varying start dates and eligibility criteria, implemented between October 2024 and January 2025.
Main Outcomes and Measures
Effectiveness, expressed as hospitalizations averted (ΔE), and incremental costs (ΔC) were estimated from the Italian National Health Service perspective. Cost-effectiveness ratios (CERs = ΔC/ΔE) were calculated for each center.
Results
During the 2024 to 2025 season, 5924 RSV-related hospitalizations were recorded in children 18 years and younger across 19 centers. Observed admissions were consistently lower than model-based counterfactual predictions in most centers. Immunization averted between 6 and 151 admissions per center, corresponding to a rate of 83 and 1162 per 100 000 children. Incremental costs were negative in most centers, indicating cost savings ranging from −€10 924 (US $12 562.60) to −€266 954 (US $306 997.10) per center. Corresponding cost-effectiveness ratios were negative (−€1071 [US $1231.65] and −€1682 [(US $1934.30]), reflecting a cost-saving intervention. In 2 centers with late initiation and restricted eligibility, immunization was associated with higher costs relative to the number of hospitalizations prevented, with incremental costs of €19 715 (US $22 672.25) and €81 454 (US $93 672.10). Sensitivity analyses confirmed the robustness of results.
Conclusions and Relevance
Results of this Italian multicenter, real-world economic evaluation suggest that nirsevimab immunization was both clinically effective and cost saving from a health system perspective. Timing and eligibility of immunization strongly influenced cost-effectiveness, highlighting the importance of early and broad rollout strategies to maximize clinical and economic benefits.
Introduction
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children, and one of the main causes of pediatric hospital admissions in Europe and worldwide.1,2 The clinical and economic burden of RSV is substantial, with hospitalizations, intensive care admissions, and long-term sequelae such as recurrent wheezing imposing significant pressure on health care systems.3,4,5,6 Until recently, preventive options were limited to palivizumab, restricted to high-risk infants due to cost and feasibility.7 Nirsevimab, a long-acting monoclonal antibody, has demonstrated high efficacy in clinical trials and effectiveness in real-world implementation studies, offering a single-dose seasonal protection for all infants.8,9,10,11,12,13,14,15,16,17 Several model-based economic evaluations suggest that nirsevimab may be cost-effective or cost saving.18,19,20,21,22,23,24 However, such analyses may not fully capture routine clinical practice, and projected economic outcomes may differ after implementation.25,26 This distinction is particularly relevant for RSV prevention strategies, where hospitalization burden and timing of immunization campaigns vary across countries.27 To date, real-world cost-effectiveness evidence for nirsevimab based on observed hospitalization outcomes across heterogeneous implementation strategies remains limited in Europe, particularly at a multicenter or national scale.28 This study aimed to evaluate the real-world cost-effectiveness of nirsevimab in preventing RSV-associated hospitalizations across 19 Italian pediatric hospitals, providing multicenter evidence to inform immunization strategies.
Methods
Study Design and Setting
We conducted a multicenter, observational, cost-effectiveness analysis across 19 Italian pediatric hospitals (Table 1).The study combined an epidemiological evaluation of RSV-associated hospitalizations with an economic analysis comparing costs and effectiveness of nirsevimab immunization vs a counterfactual scenario of no immunization. The study was based exclusively on fully anonymized and aggregated hospital administrative data. No individual-level clinical information or patient identifiers were accessed. In accordance with national regulations29 and international ethical standards,30 neither individual informed consent nor formal ethics committee approval was required. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guidelines (eTables 1 and 2 in Supplement 1)
Table 1. Characteristics of Regional Immunization Campaigns Against Respiratory Syncytial Virus (RSV) in 19 Italian Pediatric Centersa.
| Group | Geographical area | Region | Center | Campaign’s target (born after) date | Campaign’s start date |
|---|---|---|---|---|---|
| 1 | North-West | Piedmont | Turin, Alessandria | 01/01/2024 | 01/11/2024 |
| 1 | North-West | Lombardy | Brescia, Milan | ||
| 1 | North-East | Veneto | Padova | ||
| 1 | Islands | Sicily | Messina | ||
| 1 | Center | Tuscany | Florence, Pisa | 01/04/2024 | 01/11/2024 |
| 1 | North-East | Friuli Venezia Giulia | Trieste | ||
| 1 | South | Apulia | Bari | 01/07/2024 | 01/11/2024 |
| 1 | South | Campania | Naples, Salerno, Caserta, Avellino | 01/08/2024 | 01/11/2024 |
| 2 | North-East | Emilia Romagna | Bologna | 01/09/2024 | 01/10/2024 |
| 3 | North-West | Liguria | Genoa | 01/07/2024 | 01/12/2024 |
| 3 | Center | Marche | Ancona | 01/10/2024 | 01/12/2024 |
| 4 | South | Abruzzo | Chieti, Pescara | 01/01/2025 | 01/01/2025 |
Abbreviations: Alessandria, Cesare Arrigo Children’s Hospital; Ancona, Salesi Children’s Hospital; Avellino, San Giuseppe Moscati Hospital; Bari, Bari University Hospital; Bologna, Bologna University Hospital IRCCS; Brescia, Brescia Children’s Hospital; Caserta, AORN Sant’Anna e San Sebastiano; Chieti, S.S. Annunziata Hospital; Florence, Meyer Children’s Hospital IRCCS; Genoa, IRCCS Giannina Gaslini Institute; Messina, Gaetano Martino University Hospital; Milan, IRCCS Ca’ Grande Ospedale Maggiore; Naples, AORN Santobono Pausilipon; Padova, Padova University Hospital; Pescara, Pescara Hospital; Pisa, Pisa University Hospital; Salerno, AOU Ruggi d’Aragona; Turin, Regina Margherita Children’s Hospital; Trieste, Burlo Garofalo Children’s Hospital IRCCS.
Centers were grouped according to the start date of the immunization campaign. Full names of participating hospitals are reported below each center for reference.
During the 2024 to 2025 season, Italy implemented its first nirsevimab immunization campaign through a regionally coordinated approach. Each region defined its own eligibility criteria and start date, resulting in substantial heterogeneity across the country. Some regions offered immunization only to infants born during the RSV season, whereas others implemented catchup campaigns that also included infants born earlier in the same year, with birth cutoffs ranging from January to September 2024. Campaigns began between October 2024 and January 2025.
Study Population and Data Sources
RSV-related hospitalizations were identified from hospital discharge records using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes: acute RSV bronchiolitis (466.11), RSV infection (079.6), and RSV pneumonia (480.1).4,5 RSV-specific ICD-9-CM codes were used to ensure diagnostic specificity across centers. In participating centers, etiological diagnosis of respiratory infections is routinely supported by polymerase chain reaction–based assays; however, individual-level laboratory results were not accessed or linked. Data were collected between October 1, 2022, and March 31, 2025, thereby ensuring at least 2 full precampaign seasons. The period overlapping the COVID-19 pandemic was excluded due to atypically low RSV circulation, which could distort baseline estimates.4,5 All patients younger than 18 years were included to capture the full pediatric burden and assess population-level effects. The size of the resident population was extracted from the National Institute of Statistics (ISTAT) database.
Costs were assessed from the perspective of the Italian National Health Service. Direct medical costs included the following:
Unit costs per hospitalization, derived from regional Diagnosis-Related Group tariffs, which represent standardized reimbursement rates used by the Italian National Health Service for inpatient care and provide bundled estimates of hospitalization costs, including diagnostic procedures, treatments, and inpatient resource use.
The cost of the immunization program, initially available at the regional level and allocated proportionally to each center according to the size of the resident eligible population in the corresponding province on January 1, 2025. The unit acquisition cost of nirsevimab was €230 (US $264.50) per dose during the 2024 to 2025 season.
Statistical Analysis
The data consisted of monthly counts of hospitalizations, aggregated by center, year, and month, for each ICD-9-CM diagnostic code. For analytical purposes, participating centers were categorized into 4 groups according to the timing of nirsevimab campaign initiation (group 1, October 2024; group 2, November 2024; group 3, December 2024; and group 4, January 2025) (Table 1). For each group and RSV diagnostic category, Poisson regression models were fitted to the number of hospitalizations during the precampaign period. These models were used to estimate the expected number of hospitalizations in the absence of immunization. Models were adjusted for calendar time to capture seasonal patterns using a Fourier series (sine and cosine terms with annual periodicity) and for center to control for differences in admission practices, catchment areas, or population characteristics. To account for differences in the size of the population at risk across centers and over time, models included an offset term defined as the logarithm of the resident population aged 0 to 18 years. The primary outcome was the effectiveness of immunization, defined as the number of hospitalizations averted during the 2024 to 2025 season, calculated as the difference between model-based counterfactual admission predictions, representing expected values in the absence of immunization, and observed admissions (ΔE).
Economic Evaluation
Incremental costs (ΔC) were defined as the difference between immunization and no-immunization scenarios. The cost-effectiveness ratio (CER) was computed for each center and region as ΔC divided by ΔE. A negative CER indicates that immunization is dominant: it both saves costs and prevents hospitalizations. To quantify statistical uncertainty, 1000 bootstrap resamples from the Poisson model predictions were used and point estimates and 95% uncertainty intervals (UIs) were estimated using the median CER and 2.5 and 97.5 percentiles of the resulting empirical distribution.
Sensitivity Analyses
Robustness was explored through deterministic sensitivity analyses varying parameters on unit costs for hospitalization and for the immunization program and on the estimated number of hospitalizations averted. Six scenarios were considered as follows: (1) a 20% increase in both hospitalization and immunization costs, (2) a 20% decrease in both hospitalization and immunization costs, (3) a 40% decrease in immunization costs, (4) a 20% reduction in hospitalizations in the absence of immunization, (5) a 20% increase in hospitalizations in the absence of immunization, and (6) a combination of higher costs (hospitalization and immunization) and a 20% reduction in hospitalizations in the absence of immunization. This allowed assessment of the stability of cost-effectiveness under plausible variations in epidemiological and economic assumptions with a wide geographic distribution.
As an additional methodological sensitivity analysis, Poisson models were refitted using center-level random intercepts instead of fixed center indicators, allowing for partial pooling across centers. Results from this analysis were compared with the main fixed-effects specification to assess the robustness of the estimated number of hospitalizations averted.
Results
Hospitalizations Averted (Effectiveness)
Between October 1, 2022, and March 31, 2025, a total of 5924 RSV-related hospitalizations were recorded across the 19 participating centers in children 18 years and younger (eFigure in Supplement 1). During the 2024 to 2025 season, observed admissions were consistently lower than model-based counterfactual predictions in most centers, as illustrated in Figure 1. The estimated number of averted hospitalizations (ΔE) ranged from 6 (95% UI, −4 to 18) with a rate of 83 per 100 000 (95% UI −55 to 258) in Caserta (Campania, South) to 151 (95% UI, 129-176) with a rate of 1162 per 100 000 (95% UI, 995-1358) in Turin (Piedmont, North-West) (Table 2). Large reductions were observed in centers such as Florence (Toscana, Center) with 117 (95% UI, 96-142; 1966 per 100 000, 95% UI, 1605-2377) averted hospitalizations, Naples (Campania, South; 110, 95% UI, 71-154; 481 per 100 000, 95% UI, 309-675), Ancona (Marche, Center; 75; 95% UI, 55-102; 2927 per 100 000, 95% UI, 2171-3992). Effectiveness estimates showed greater uncertainty in Genoa (Liguria, North-West; 497 per 100 000, 95% UI, −256 to 1516) and Caserta (Table 2). In contrast, ΔE was negative in Chieti (Abruzzo, Center; −12, 95% UI, −23 to 6; −556 per 100 000, 95% UI, −1087 to 275) and Pescara (Abruzzo, Center; −47, 95% UI, −64 to −22; −2573 per 100 000, 95% UI, −3494 to −1209), indicating more admissions than expected in the absence of immunization (Table 2). Excluding centers with late campaign initiation, the averted admissions corresponded to approximately 20% to 150% of the mean number of RSV-related hospitalizations recorded in prior winter seasons (eTable 3 in Supplement 1).
Figure 1. Line and Scatter Plot Showing Trends in Respiratory Syncytial Virus (RSV)–Related Hospitalizations by Diagnostic Category and Immunization Group.
Monthly counts of hospitalizations for acute RSV bronchiolitis (A), RSV infection (B), and RSV pneumonia (C) across 19 Italian pediatric centers, from October 2022 to March 2025. Solid lines represent model-based counterfactual predictions in the absence of immunization, with shaded areas indicating 95% CIs. Dots represent observed admissions. Groups reflect the timing and eligibility of regional immunization strategies as shown in Table 1. Jan indicates January.
Table 2. Avoided Hospitalizations, Incremental Hospitalization Costs, and Cost-Effectiveness Ratios by Centera.
| Centers | Avoided hospitalizationsb | Avoided hospitalization costsc | CER, € per hospitalization preventedc | |
|---|---|---|---|---|
| Count | Rate | |||
| Naples | 110 (71 to 154) | 481 (309 to 675) | −182 871 (−262 014 to −113 140) | −1516 (−1544 to −1479) |
| Salerno | 30 (18 to 45) | 409 (241 to 613) | −53 862 (−80 575 to −31 963) | −1616 (−1636 to −1591) |
| Caserta | 6 (−4 to 18) | 83 (−55 to 258) | −10924 (−32 853 to 6363) | −1071 (−1341 to 247) |
| Avellino | 11 (6 to 19) | 461 (246 to 762) | −20 754 (−33 687 to −11 486) | −1692 (−1703 to −1679) |
| Trieste | 30 (23 to 40) | 2233 (1672 to 2946) | −53 050 (−69 903 to −39 773) | −1710 (−1712 to −1708) |
| Chieti | −12 (−23 to 6) | −556 (−1087 to 275) | 19 715 (−12 154 to 39 869) | −1717 (−1754 to −1626) |
| Pescara | −47 (−64 to −22) | −2573 (−3494 to −1209) | 81 454 (36 168 to 111 754) | −1734 (−1747 to −1715) |
| Bologna | 52 (20 to 123) | 791 (304 to 1859) | −89 044 (−218 933 to −32 044) | −1635 (−1680 to −1592) |
| Messina | 63 (51 to 77) | 1732 (1400 to 2129) | −109 581 (−134 895 to −88 462) | −1685 (−1689 to −1680) |
| Bari | 61 (48 to 78) | 775 (605 to 980) | −110 222 (−139 099 to −86 358) | −1672 (−1679 to −1664) |
| Ancona | 75 (55 to 102) | 2927 (2171 to 3992) | −127 937 (−176 406 to −93 954) | −1704 (−1712 to −1696) |
| Turin | 151 (129 to 176) | 1162 (995 to 1358) | −266 954 (−312 156 to −228 295) | −1682 (−1687 to −1678) |
| Alessandria | 39 (26 to 54) | 1830 (1224 to 2544) | −61 986 (−88 468 to −39 533) | −1534 (−1564 to −1499) |
| Padua | 54 (39 to 71) | 941 (680 to 1249) | −89 208 (−120 185 to −62 989) | −1553 (−1576 to −1528) |
| Genoa | 23 (−12 to 71) | 497 (−256 to 1516) | −39 205 (−125 169 to 23 838) | −1569 (−1649 to −1305) |
| Florence | 117 (96 to 142) | 1966 (1605 to 2377) | −200 756 (−243 731 to −163 042) | −1660 (−1666 to −1653) |
| Pisa | 8 (2 to 17) | 325 (92 to 641) | −14 671 (−29 004 to −4102) | −1458 (−1529 to −1324) |
| Milan | 59 (37 to 86) | 275 (173 to 397) | −109 130 (−156 773 to −69 412) | −1451 (−1491 to −1402) |
| Brescia | 45 (28 to 64) | 534 (332 to 772) | −78 085 (−113 317 to −48 234) | −1553 (−1579 to −1518) |
Values are point estimates with 95% uncertainty intervals in parentheses.
Avoided hospitalizations = number of hospitalizations assuming no immunization − number of hospitalizations under the vaccination strategy; incremental costs = costs due to hospitalizations under the vaccination strategy − costs due to hospitalizations assuming no vaccination.
Conversion rate: 1 Euro = 1.15 US dollars (source: Bloomberg.com as of March 16, 2026).
Cost-Effectiveness
Incremental costs for hospitalizations (ΔC) were negative in most centers, confirming cost savings. Incremental costs were negative in most centers, indicating cost savings ranging from −€10 924 (US $12 562.60) to −€266 954 (US $306 997.10) per center. For example, the intervention generated net savings of €266 954 (US $306 997.10; 95% UI, €228 295 [US $262 539.25] to €312 156 [US $358 979.40]) in Turin, €200 756 (US $230 869.40; 95% UI, €163 042 [US $187 498.30] to €243 731 [US $280 290.65]) in Florence, and €182 871 (US $210 301.65; 95% UI, €262 014 [US $301 316.10] to €113 140 [US $130 111.00]) in Naples (Table 2). Corresponding CERs were −€1682 (US $1934.30), −€1660 (US $1909.00), and −€1516 (US $1743.40) per hospitalization prevented, respectively. In nearly all centers, CERs were negative due to positive avoided hospitalizations and negative avoided costs, reflecting savings per hospitalization averted rather than costs (Table 2 and Figure 2). Only Chieti (€19 715 [US $22 672.25]; 95% UI, −€12 154 [US $13 977.10] to €39 869 [US $45 849.35]) and Pescara (€81 454 [US $93 672.10]; 95% UI, €36 168 [US $41 593.20] to €11 754 [US $13 517.10]) showed positive incremental costs combined with negative ΔE, indicating that immunization was dominated by the counterfactual scenario (Table 2 and Figure 2). Larger uncertainty in CER estimates were observed in Caserta (−€1071 [US $1231.65]; 95% UI, −€1341 [US $1542.15] to €247 [US $284.05]) and Genoa (−€1569 [US $1804.35]; 95% UI, −€1649 [US $1896.35] to −€1305 [1500.75]) (Table 2 and Figure 2).
Figure 2. Point-Estimate Plot Displaying Cost-Effectiveness Ratios (CERs) of Nirsevimab Immunization by Center.
Values are point estimates with 95% uncertainty intervals. Negative CERs indicate savings per hospitalization averted; in Chieti and Pescara, outcomes were dominated despite formally negative CER values.
Cost-effectiveness acceptability curves (CEACs) were calculated for each center (data not shown). For most centers, the CEACs were flat at 1, indicating that the vaccination program was consistently cost saving and effective, with a probability of being cost-effective equal to 100% across all willingness-to-pay thresholds. Exceptions were observed for the Chieti and Pescara centers, where incremental costs were positive while the number of averted hospitalizations was negative. In these cases, the CEACs were flat at 0, reflecting that the intervention was dominated (ie, more costly, and less effective) and, therefore, had a 0 probability of being cost-effective.
Regional Variability
Marked variability in avoided hospitalization and avoided hospitalization costs was observed by visual inspection when centers were considered according to the regional immunization strategies under which they operated (Table 2 and Figure 2). Centers in regions that initiated campaigns early with broad eligibility criteria (eg, Piedmont, Tuscany) consistently showed negative CERs, reflecting cost savings per hospitalization prevented (Table 1 and Table 2). Conversely, centers in regions with more restrictive eligibility, despite starting in November (eg, Campania, Apulia), showed less consistent savings (Table 1 and Table 2). In Abruzzo, where the campaign began only in January 2025 and was restricted to infants born thereafter, CERs were unfavorable, with immunization dominated by the counterfactual scenario (Table 1 and Table 2).
Sensitivity Analyses
Results remained robust across sensitivity analyses (Figure 3 and eTable 4 in Supplement 1). When hospitalization and immunization costs were varied by ±20%, or when optimistic and pessimistic bounds of ΔE were used, nirsevimab remained cost saving in the majority of centers. The effect was consistent across scenarios, assuming reductions or increases in expected hospitalizations. However, uncertainty persisted in Caserta, and outcomes in Chieti and Pescara remained dominant (Figure 3 and eTable 4 in Supplement 1). In sensitivity analyses using Poisson models with center-level random intercepts, the overall direction and magnitude of the estimated reduction in hospitalizations were consistent with the main analysis. However, center-specific estimates showed greater variability, particularly for centers with smaller populations or shorter time series, reflecting the expected shrinkage and redistribution of effects under the random-effects specification. Given the limited number of centers and our focus on center-specific estimates, the fixed-effects model was retained as the primary analysis (eTable 5 in Supplement 1).
Figure 3. Sensitivity Analysis Heat Map.
Scenarios are as follows: (1) +20% hospitalization and immunization costs, (2) −20% hospitalization and immunization costs, (3) −40% immunization costs, (4) 20% reduction in expected hospitalizations without immunization, (5) 20% increase in expected hospitalizations without immunization, and (6) combined scenario with higher immunization costs and a 20% reduction in expected hospitalizations without immunization.
Discussion
Main Findings
This multicenter study provides the first, to our knowledge, real-world evidence on the cost-effectiveness of nirsevimab immunization in Europe. Across 19 Italian pediatric centers, immunization was associated with substantial reductions in RSV-related hospitalizations, and in most centers the intervention was dominant, yielding both greater effectiveness and lower costs. Only Chieti and Pescara showed dominant results, likely reflecting late campaign initiation and limited eligible populations.
CER Results and Immunization Strategies
Although our analyses were conducted at the center level, immunization strategies were determined regionally, and the results observed in each center therefore reflect the approach adopted in its region. Centers located in regions that initiated campaigns in November 2024 with broad eligibility criteria showed consistently favorable CERs, with savings per hospitalization prevented. By contrast, when eligibility was limited to infants born after July or August 2024, despite starting at the same time, it achieved narrower protection and less consistent cost savings. Centers in regions that launched the immunization campaign in October with a September cutoff showed dominance but with wide uncertainty. Centers where campaigns began in December showed more heterogeneous results, with favorable point estimates but greater uncertainty, likely reflecting the reduced opportunity for protection as part of the epidemic peak had already occurred. Finally, centers where the campaign started in January 2025 and was restricted to infants born thereafter showed dominant results, with both higher costs and excess hospitalizations with immunization (negative ΔE), rather than simply fewer hospitalizations averted. These findings suggest that while the size of the eligible target population influences absolute impact, the timing of campaign initiation was the main determinant of cost-effectiveness.
Comparison With Other Studies
Our findings are consistent with previous Italian and international modeling studies, while providing the first, to our knowledge, real-world multicenter validation. During the study period, maternal RSV vaccination was not implemented in Italy, and no regions had introduced maternal immunization programs; therefore, the observed effects reflect the impact of infant nirsevimab immunization alone. In Italy, Marcellusi et al3 and Bini et al18 estimated that universal infant immunization with nirsevimab would be cost-effective at an economically justifiable price of €267 (US $307.05) to €400 (US $460.00) per dose. Our analysis, conducted at the observed procurement cost of €230 (US $264.50) shows that the intervention was not only cost-effective but dominant in most centers, confirming and strengthening those projections. Polistena et al21 further suggested that combining maternal vaccination with infant immunization could improve efficiency, an approach that warrants evaluation in future real-world settings. International studies similarly support the clinical and economic potential of nirsevimab. In Canada, Shoukat et al22 reported favorable cost-effectiveness estimates for nirsevimab strategies among infants, corresponding to a cost of approximately CAD$290 (US $211.55) per dose. Similarly, Zeevat et al20 reported a threshold of €220 (US $253.00) per dose in pediatric populations in the Netherlands. Our findings, obtained at a cost of €230 (US $264.50) per dose, are closely aligned with these estimates. By contrast, US analyses found less favorable cost-effectiveness at higher list prices, often favoring maternal vaccination.19,31 These US-based evaluations reported less favorable cost-effectiveness mainly due to higher hospitalization costs and drug prices. Together, these comparisons highlight that nirsevimab economic value depends on local pricing and timing of implementation, but the direction of evidence is consistent: the intervention is highly effective, and as our study results suggest, already cost saving in practice.
Strengths and Limitations
The strengths of our study include its multicenter design, use of administrative hospitalization data across a wide geographic distribution, and rigorous statistical modeling that accounted for seasonality and uncertainty. Importantly, the analysis was based on observed data, providing real-world validation of earlier modeling studies. Most participating hospitals were tertiary-level pediatric centers. Based on provincial population data from the ISTAT, participating centers are in provinces accounting for approximately 35% of the Italian pediatric population. This figure is likely conservative, as pediatric RSV hospitalizations are highly centralized.
In addition, some limitations should be acknowledged. The study relied on ICD-9-CM discharge codes as a proxy for RSV infection, with case identification restricted to RSV-specific diagnostic codes to prioritize specificity over sensitivity. Although RSV-specific codes are generally assigned in routine clinical practice based on virological testing, individual laboratory results were not available for validation at the patient level, which leading to misclassification and conservative effect estimates. Additional limitations include the use of real-world data that are susceptible to information bias, the use of regional tariffs and proportional allocation of program costs that may not have captured all local variations, and the restriction of the analysis to direct medical costs, without considering indirect consequences. Prior studies have shown that parental productivity loss during infant hospitalization can be substantial, and early-life RSV infection has been linked to long-term sequelae such as recurrent wheezing and asthma, with associated health care costs.19,32,33 Excluding these factors may underestimate the economic value of nirsevimab immunization. Moreover, we included all children 18 years and younger to assess the hospital-wide impact of an infant-targeted strategy; age-stratified analyses were not feasible because only aggregated administrative data were available, limiting comparability with studies restricted to infants. Finally, given the time series structure of the data, residual temporal autocorrelation cannot be completely excluded. However, calendar time was explicitly modeled using flexible seasonal terms (Fourier series), capturing the strong annual cyclic pattern of RSV hospitalizations. In this context, Poisson regression was well suited for count data observed across multiple centers, allowing straightforward adjustment for population size, center-specific effects, and seasonality over a relatively short observation period.
Conclusions
Findings of this economic evaluation of RSV-related hospitalizations in 19 pediatric hospitals in Italy suggest that nirsevimab immunization was cost saving and clinically effective when campaigns were initiated before the epidemic season. Delayed implementation or restrictive eligibility substantially reduced benefits, underscoring the need for early and coordinated strategies. At the observed procurement cost, nirsevimab was dominant in most settings, supporting its inclusion in national immunization programs. Although our study did not evaluate maternal vaccination, future research should assess the potential added benefit of integrated strategies, particularly in settings where delayed implementation or restrictive eligibility reduces the impact of infant immunization alone.
eFigure. Map Showing Participating Pediatric Centers and Regional Distributions of the Population Eligible for Immunization Across Italy, Providing Geographical Context to the Cost-Effectiveness Heterogeneity
eTable 1. STROBE Checklist (2023 Version)—Fully Completed With Page/Paragraph References to Demonstrate Adherence to Observational Study Reporting Standards
eTable 2. CHEERS 2022 Checklist—Completed With References to Manuscript Sections to Ensure Compliance With Health Economic Evaluation Reporting Standards
eTable 3. Averted RSV-Related Hospitalizations During the 2024-2025 Season Relative to Historical Winter Averages, by Center
eTable 4. Sensitivity Analyses of Cost-Effectiveness Ratios (CERs) by Center Under 6 Alternative Scenarios
eTable 5. Sensitivity Analysis of Avoided Hospitalizations by Center Using Poisson Models With Center-Level Random Intercepts
Data Sharing Statement.
References
- 1.Li Y, Wang X, Blau DM, et al. ; Respiratory Virus Global Epidemiology Network; RESCEU investigators . Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 2022;399(10340):2047-2064. doi: 10.1016/S0140-6736(22)00478-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Attaianese F, Guiducci S, Trapani S, et al. Reshaping our knowledge: advancements in understanding the immune response to human respiratory syncytial virus. Pathogens. 2023;12(9):1118. doi: 10.3390/pathogens12091118 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Marcellusi A, Bini C, Muzii B, et al. Economic and clinical burden associated with respiratory syncytial virus and impact of universal immunization with nirsevimab in Italy. Glob Reg Health Technol Assess. 2025;12(1):16-28. doi: 10.33393/grhta.2025.3182 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Palmas G, Trapani S, Agosti M, et al. ; Associazione Ospedali Pediatrici Italiani (AOPI) Network . Disrupted seasonality of respiratory viruses: retrospective analysis of pediatric hospitalizations in Italy from 2019 to 2023. J Pediatr. 2024;268:113932. doi: 10.1016/j.jpeds.2024.113932 [DOI] [PubMed] [Google Scholar]
- 5.Indolfi G, Resti M, Zanobini A; Associazione Ospedali Pediatrici Italiani Research Group on Bronchiolitis . Outbreak of respiratory syncytial virus bronchiolitis in Italy. Clin Infect Dis. 2022;75(3):549-550. doi: 10.1093/cid/ciac120 [DOI] [PubMed] [Google Scholar]
- 6.Bozzola E, Ciarlitto C, Guolo S, et al. Respiratory syncytial virus bronchiolitis in infancy: the acute hospitalization cost. Front Pediatr. 2021;8:594898. doi: 10.3389/fped.2020.594898 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee . Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420. doi: 10.1542/peds.2014-1665 [DOI] [PubMed] [Google Scholar]
- 8.Griffin MP, Yuan Y, Takas T, et al. ; Nirsevimab Study Group . Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020;383(5):415-425. doi: 10.1056/NEJMoa1913556 [DOI] [PubMed] [Google Scholar]
- 9.Hammitt LL, Dagan R, Yuan Y, et al. ; MELODY Study Group . Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022;386(9):837-846. doi: 10.1056/NEJMoa2110275 [DOI] [PubMed] [Google Scholar]
- 10.Assad Z, Romain AS, Aupiais C, et al. Nirsevimab and hospitalization for RSV bronchiolitis. N Engl J Med. 2024;391(2):144-154. doi: 10.1056/NEJMoa2314885 [DOI] [PubMed] [Google Scholar]
- 11.López-Lacort M, Muñoz-Quiles C, Mira-Iglesias A, et al. Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024. Euro Surveill. 2024;29(6):2400046. doi: 10.2807/1560-7917.ES.2024.29.6.2400046 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Wadia U, Moore HC, Richmond PC, et al. Effectiveness of nirsevimab in preventing RSV-hospitalization among young children in Western Australia 2024. J Infect. 2025;90(4):106466. doi: 10.1016/j.jinf.2025.106466 [DOI] [PubMed] [Google Scholar]
- 13.Attaianese F, Trapani S, Agostiniani R, et al. Effectiveness of a targeted infant RSV immunization strategy (2024-2025): a multicenter matched case-control study in a high-surveillance setting. J Infect. 2025;91(3):106600. doi: 10.1016/j.jinf.2025.106600 [DOI] [PubMed] [Google Scholar]
- 14.Ares-Gómez S, Mallah N, Santiago-Pérez MI, et al. ; NIRSE-GAL study group . Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalization for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study. Lancet Infect Dis. 2024;24(8):817-828. doi: 10.1016/S1473-3099(24)00215-9 [DOI] [PubMed] [Google Scholar]
- 15.Brault A, Pontais I, Enouf V, et al. Effect of nirsevimab on hospitalizations for respiratory syncytial virus bronchiolitis in France, 2023-2024: a modeling study. Lancet Child Adolesc Health. 2024;8(10):721-729. doi: 10.1016/S2352-4642(24)00143-3 [DOI] [PubMed] [Google Scholar]
- 16.Carbajal R, Boelle PY, Pham A, et al. Real-world effectiveness of nirsevimab immunization against bronchiolitis in infants: a case-control study in Paris, France. Lancet Child Adolesc Health. 2024;8(10):730-739. doi: 10.1016/S2352-4642(24)00171-8 [DOI] [PubMed] [Google Scholar]
- 17.Moline HL, Toepfer AP, Tannis A, et al. ; New Vaccine Surveillance Network Collaborators . Respiratory syncytial virus disease burden and nirsevimab effectiveness in young children from 2023-2024. JAMA Pediatr. 2025;179(2):179-187. doi: 10.1001/jamapediatrics.2024.5572 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Bini C, Marcellusi A, Cazzato D, et al. Cost-Effectiveness analysis of nirsevimab for the prevention of respiratory syncytial virus among Italian infants. Clin Drug Investig. 2025;45(6):347-361. doi: 10.1007/s40261-025-01437-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Hutton DW, Prosser LA, Rose AM, et al. Cost-effectiveness of nirsevimab for respiratory syncytial virus in infants and young children. Pediatrics. 2024;154(6):e2024066461. doi: 10.1542/peds.2024-066461 [DOI] [PubMed] [Google Scholar]
- 20.Zeevat F, van der Pol S, Kieffer A, Postma MJ, Boersma C. Cost-effectiveness analysis of nirsevimab for preventing respiratory syncytial virus-related lower respiratory tract disease in Dutch infants: an analysis including all-infant protection. Pharmacoeconomics. 2025;43(5):569-582. doi: 10.1007/s40273-025-01469-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Polistena B, Midulla F, Sotgiu G, d’Angela D, Di Virgilio R, Spandonaro F. complementary strategy of maternal immunization with RSVpreF vaccine and monoclonal antibodies for the prevention of respiratory syncytial virus among Italian infants: a cost-effectiveness assessment. Infect Dis Ther. 2025;14(8):1883-1897. doi: 10.1007/s40121-025-01193-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Shoukat A, Abdollahi E, Galvani AP, Halperin SA, Langley JM, Moghadas SM. Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of respiratory syncytial virus disease among infants in Canada: a simulation study. Lancet Reg Health Am. 2023;28:100629. doi: 10.1016/j.lana.2023.100629 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Gebretekle GB, Yeung MW, Ximenes R, et al. Cost-effectiveness of RSVpreF vaccine and nirsevimab for the prevention of respiratory syncytial virus disease in Canadian infants. Vaccine. 2024;42(21):126164. doi: 10.1016/j.vaccine.2024.126164 [DOI] [PubMed] [Google Scholar]
- 24.Bugden S, Mital S, Nguyen HV. Cost-effectiveness of nirsevimab and maternal RSVpreF for preventing respiratory syncytial virus disease in infants across Canada. BMC Med. 2025;23(1):102. doi: 10.1186/s12916-025-03928-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Newall AT, Reyes JF, Wood JG, McIntyre P, Menzies R, Beutels P. Economic evaluations of implemented vaccination programs: key methodological challenges in retrospective analyses. Vaccine. 2014;32(7):759-765. doi: 10.1016/j.vaccine.2013.11.067 [DOI] [PubMed] [Google Scholar]
- 26.Drolet M, Bénard É, Jit M, Hutubessy R, Brisson M. Model comparisons of the effectiveness and cost-effectiveness of vaccination: a systematic review of the literature. Value Health. 2018;21(10):1250-1258. doi: 10.1016/j.jval.2018.03.014 [DOI] [PubMed] [Google Scholar]
- 27.Aricò MO, Accomando F, Trotta D, et al. Uneven implementation of nirsevimab prophylaxis resulted in nonuniform reductions in RSV-related hospitalizations in Italy. Infect Dis Rep. 2025;17(5):115. doi: 10.3390/idr17050115 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Lastrucci V, Pacifici M, Alderotti G, et al. The impact of nirsevimab prophylaxis on RSV hospitalizations: a real-world cost-benefit analysis in Tuscany, Italy. Front Public Health. 2025;13:1604331. doi: 10.3389/fpubh.2025.1604331 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Gazzetta Ufficiale della Repubblica Italiana . Italian Personal Data Protection Code: decree No. 196 of June 30, 2003, amended by legislative decree No. 101 of August 10, 2018. Article in Italian. Accessed March 11, 2026. https://www.gazzettaufficiale.it/dettaglio/codici/datiPersonali
- 30.European Parliament and Council of the European Union . Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data. Accessed March 11, 2026. https://eur-lex.europa.eu/eli/reg/2016/679/oj
- 31.Nguyen D, Lee H, Pavia AT, Nelson RE, Samore M, Chaiyakunapruk N. Optimizing timing for respiratory syncytial virus prevention interventions for infants. JAMA Netw Open. 2025;8(7):e2522779. doi: 10.1001/jamanetworkopen.2025.22779 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360(6):588-598. doi: 10.1056/NEJMoa0804877 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Binns E, Tuckerman J, Licciardi PV, Wurzel D. Respiratory syncytial virus, recurrent wheeze and asthma: a narrative review of pathophysiology, prevention and future directions. J Paediatr Child Health. 2022;58(10):1741-1746. doi: 10.1111/jpc.16197 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure. Map Showing Participating Pediatric Centers and Regional Distributions of the Population Eligible for Immunization Across Italy, Providing Geographical Context to the Cost-Effectiveness Heterogeneity
eTable 1. STROBE Checklist (2023 Version)—Fully Completed With Page/Paragraph References to Demonstrate Adherence to Observational Study Reporting Standards
eTable 2. CHEERS 2022 Checklist—Completed With References to Manuscript Sections to Ensure Compliance With Health Economic Evaluation Reporting Standards
eTable 3. Averted RSV-Related Hospitalizations During the 2024-2025 Season Relative to Historical Winter Averages, by Center
eTable 4. Sensitivity Analyses of Cost-Effectiveness Ratios (CERs) by Center Under 6 Alternative Scenarios
eTable 5. Sensitivity Analysis of Avoided Hospitalizations by Center Using Poisson Models With Center-Level Random Intercepts
Data Sharing Statement.
