Video Abstract
This study assesses the effectiveness of nirsevimab, a monoclonal antibody, in preventing medically attended respiratory syncytial virus-lower respiratory tract infections (RSV-LRTIs) in a large primary care network in Spain, in both overall and catch-up infants aged younger than 10 months.
The 2023–2024 immunization campaign with nirsevimab in Spain targeted all infants born after April 1, 2023. Those born after October 1 received it at birth in hospitals, whereas others received it through a catch-up program. The MEDIPRIM network of primary care centers recruited all infants with LRTI for RSV polymerase chain reaction testing and employed a test-negative design approach to estimate the effectiveness of nirsevimab.
The study included 160 infants; 141 (88%) of them received nirsevimab and 128 belonged to the catch-up group (88% received nirsevimab). Overall, RSV was detected in 44 infants (27.5%). Within the catch-up group, 37 (28.9%) were positive for RSV. The overall effectiveness was 75.8% (95% credible interval: 40.4–92.7), and 80.2% (95% credible interval: 44.3–95.4) in infants belonging to the catch-up group.
This study underscores the effectiveness of nirsevimab in preventing medically attended LRTI in infants in outpatient settings and emphasizes the importance of a catch-up immunization program to reduce the disease burden in primary care.
Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infections (LRTIs) in children aged younger than 5 years. Nirsevimab, a long-acting monoclonal antibody has demonstrated in clinical trials 79% of efficacy in preventing medically attended RSV-LRTI in infants.
This study demonstrates the effectiveness of nirsevimab in preventing medically attended RSV-LRTI in infants aged younger than 10 months in a large primary care network in Spain, both overall and for the catch-up group.
Introduction
Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infections (LRTIs) in children aged younger than 5 years. Hospitalizations are most common in the first year of life, particularly within the initial 3 months,1–3 whereas the highest incidence, notably bronchiolitis, arises in the second and third quarters of life.4
RSV infection compromises the physical barrier of airway epithelial tissue, triggering inflammatory responses, exacerbating airway hyper-responsiveness, and inducing airway remodeling.5 Consequently, early RSV-LRTI has been linked to recurrent wheezing and subsequent asthma, with severe disease displaying a stronger association,6 although milder LRTI may also correlate with asthma.7 However, this needs further studies.8 Moreover, RSV infection may contribute to later chronic obstructive pulmonary disease by promoting airway inflammation and remodeling, inducing oxidative stress and DNA damage, and fostering biofilm formation.9,10
Thus, preventive measures must target not only severe cases and hospitalizations, which bear the brunt of the disease burden during the acute phase, but also milder LRTI, given their high frequency of presentation,11 and their potential for significant bronchial damage complications.
Nirsevimab (Beyfortus, AstraZeneca/Sanofi Pasteur), a single-dose, long-acting monoclonal antibody targeting the highly conserved site 0 of the prefusion protein of RSV,12 has shown 79% efficacy in preventing RSV-LRTI in infants for at least 1 RSV season.13–15
The Spanish national immunization program incorporated RSV prophylaxis with this monoclonal antibody in September 2023,16 achieving an uptake of approximately 90% in our area.17 The program targeted the following 3 groups with high risk of severe RSV infection who were classified depending on their birth date and risk conditions: infants born during the immunization campaign (seasonal group), infants who were aged younger than 6 months at the start of the campaign (ie, infants born between April 1 and October 2023; catch-up group), and infants aged 6–24 months (ie, born between October 1, 2021, and March 31, 2023) with high-risk conditions at the start of the campaign. The seasonal group received nirsevimab after delivery, before discharge, whereas the 2 other groups received it at their primary care (PC) clinics.
The first effectiveness report of nirsevimab in preventing hospitalizations was conducted in 3 Spanish regions,17 showing an effectiveness of 70.2% (95% CI: 38.3–88.5) using a test-negative design (TND), and 84.4% (95% CI: 76.8–90.0) with the screening method. A second study using health care databases, performed in another region of Spain had similar results,18 and, as others, showed a large impact in the reduction of hospitalizations.19 In the United States, with low administration coverage, it reached an effectiveness of 90%.20 However, data on effectiveness in preventing medically attended RSV-LRTIs that do not require hospitalization are lacking. This study assesses the effectiveness of nirsevimab in preventing medically attended RSV-LRTI in infants aged younger than 10–months of age in a large PC network in Spain, in both overall and catch-up group.
Methods
This TND study was carried out within the Mediterranean Infectious Diseases Primary care network (MEDIPRIM) consisting of 92 pediatricians from 57 PC centers in the Valencia and Murcia regions of Spain.
Infants born after April 1, 2023 (candidates to receive nirsevimab), attended in the participant PC centers with symptoms related to LRTI were eligible for participation. The inclusion criteria used in this study were similar to those used in the clinical trials evaluating the efficacy of nirsevimab.15 These criteria required the detection of RSV through real-time reverse-transcription polymerase chain reaction assay (PCR) and the presence of at least 1 sign of lower respiratory tract disease (rhonchi, rales, crackles, or wheeze) or apnea. Participants were excluded if symptom onset exceeded 10–days.
Clinical and demographic data were collected by the pediatricians. Nasopharyngeal and oropharyngeal samples were collected and combined in 1 tube of viral transport medium. Samples were stored refrigerated (2°–8°) at the PC center and sent every week to either the Microbiology department of Hospital Virgen de la Arrixaca in Murcia or the centralized virology laboratory of FISABIO-Public Health in Valencia. Multiplex PCR AllplexTM Respiratory Panel 1, 2 y 3 (Seegene) was performed in Murcia and an in-house multiplex real-time PCR following WHO protocols21 with the qScript XLT One-Step RT-qPCR ToughMix (Quanta BioSciences) in a Lightcycler 480II apparatus (Roche Diagnostics) was used in Valencia.
PCR positives for RSV were considered as cases and negative results for RSV (including those PCR negative and positive for other virus) as controls.
Nirsevimab administration status was obtained from the regional vaccination registries (VIS22 in Valencia and VACUSAN in Murcia).
Samples were collected during the RSV circulation period23 (ie, between November 1, 2023 [week 45], and February 29, 2024 [week 9]). Nirsevimab effectiveness and its respective 95% CIs were estimated both overall and specifically for catch-up infants by a Bayesian logistic regression. The effectiveness was calculated as (1− odds ratio) × 100%, in which the odds ratio represents the odds of testing positive for RSV given nirsevimab administration compared with the odds without nirsevimab. Noninformative priors for the model parameters were considered, ensuring that our estimations remained uninfluenced by prior assumptions. Flat priors were considered for the intercept and the coefficient related to the nirsevimab administration status. The random effects were introduced via normally distributed priors (with mean equal to 0) for the coefficients related to PC centers, allowing us to capture variability across them. To address the precision of these random effects, we specified a hyperparameter for the standard deviation, assigning it a uniform distribution from 0 to 10. All analyses were performed with the R version 4.3.3 program.
Ethical Statement
The Ethics Committees of each region approved the protocol of the study. At least 1 parent/legal guardian signed a written informed consent before the inclusion of the infant in the study.
Results
The study encompassed 160 infants, with 67% (107/160) aged at least 3 months, and most boys (102/160; 64%). Table 1 outlines the demographic characteristics of the population.
Characteristics of Infants Aged Younger Than 10 Months Born After April 1, 2023, With Lower Respiratory Tract Infections Attended in PC and Overall and for Infants Testing Positive (Cases) and Negative (Controls) for RSV in RT-PCR Results and by Nirsevimab Administration, November 2023 – January 2024 (n = 160 infants), Valencia and Murcia Regions of Spain
| Characteristic | Overall, N = 160 | RSV+ | RSV− | ||||
|---|---|---|---|---|---|---|---|
| N = 44 | Nirsevimab Administration, N = 33 | Not Nirsevimab Administration, N = 11 | N = 116 | Nirsevimab Administration, N = 108 | Not Nirsevimab Administration, N = 8 | ||
| Nirsevimab administration, n (%) | 141 (88) | 33 (75) | 108 (93) | ||||
| Sex, n (%) | |||||||
| Male | 102 (64) | 30 (68) | 23 (70) | 7 (64) | 72 (62) | 69 (64) | 3 (38) |
| Female | 58 (36) | 14 (32) | 10 (30) | 4 (36) | 44 (38) | 39 (36) | 5 (63) |
| Age at PC consultation, months, n (%) | |||||||
| 0–3 | 53 (33) | 15 (34) | 14 (42) | 1 (9.1) | 38 (33) | 35 (32) | 3 (38) |
| ≥3 | 107 (67) | 29 (66) | 19 (58) | 10 (91) | 78 (67) | 73 (68) | 5 (63) |
| Age at PC consultation, months | |||||||
| Mean (SD) | 4.60 (2.25) | 4.55 (2.04) | 4.39 (2.01) | 5.00 (2.14) | 4.62 (2.33) | 4.65 (2.29) | 4.25 (2.96) |
| Median (IQR) | 4.50 (3.00–6.00) | 4.00 (3.00–6.00) | 4.00 (3.00–6.00) | 5.00 (4.00–6.50) | 5.00 (3.00–7.00) | 5.00 (3.00–7.00) | 4.50 (2.50–5.50) |
| Range | 0.00–9.00 | 0.00–8.00 | 0.00–8.00 | 0.00–8.00 | 0.00–9.00 | 0.00–9.00 | 0.00–9.00 |
| Age at administration, n (%) | |||||||
| 0 | 47 (33) | 15 (45) | 32 (30) | ||||
| 1 | 15 (11) | 3 (9.1) | 12 (11) | ||||
| 2 | 17 (12) | 4 (12) | 13 (12) | ||||
| 3 | 16 (11) | 2 (6.1) | 14 (13) | ||||
| 4 | 26 (18) | 4 (12) | 22 (20) | ||||
| 5 | 13 (9.2) | 5 (15) | 8 (7.4) | ||||
| 6 | 7 (5.0) | 7 (6.5) | |||||
| Not administered | 19 | ||||||
| Eligible infants for preventive program, n (%) | |||||||
| Catch-up | 128 (80) | 37 (84) | 27 (82) | 10 (91) | 91 (78) | 85 (79) | 6 (75) |
| Seasonal | 32 (20) | 7 (16) | 6 (18) | 1 (9.1) | 25 (22) | 23 (21) | 2 (25) |
| Preschool siblings | 44 (28) | 14 (32) | 9 (27) | 5 (45) | 30 (26) | 30 (28) | 0 (0) |
| Daycare | 12 (7.5) | 1 (2.3) | 1 (3.0) | 0 (0) | 11 (9.5) | 9 (8.3) | 2 (25) |
| Preterm | 18 (11) | 3 (6.8) | 2 (6.1) | 1 (9.1) | 15 (13) | 14 (13) | 1 (13) |
| Characteristic | Overall, N = 160 | RSV+ | RSV− | ||||
|---|---|---|---|---|---|---|---|
| N = 44 | Nirsevimab Administration, N = 33 | Not Nirsevimab Administration, N = 11 | N = 116 | Nirsevimab Administration, N = 108 | Not Nirsevimab Administration, N = 8 | ||
| Nirsevimab administration, n (%) | 141 (88) | 33 (75) | 108 (93) | ||||
| Sex, n (%) | |||||||
| Male | 102 (64) | 30 (68) | 23 (70) | 7 (64) | 72 (62) | 69 (64) | 3 (38) |
| Female | 58 (36) | 14 (32) | 10 (30) | 4 (36) | 44 (38) | 39 (36) | 5 (63) |
| Age at PC consultation, months, n (%) | |||||||
| 0–3 | 53 (33) | 15 (34) | 14 (42) | 1 (9.1) | 38 (33) | 35 (32) | 3 (38) |
| ≥3 | 107 (67) | 29 (66) | 19 (58) | 10 (91) | 78 (67) | 73 (68) | 5 (63) |
| Age at PC consultation, months | |||||||
| Mean (SD) | 4.60 (2.25) | 4.55 (2.04) | 4.39 (2.01) | 5.00 (2.14) | 4.62 (2.33) | 4.65 (2.29) | 4.25 (2.96) |
| Median (IQR) | 4.50 (3.00–6.00) | 4.00 (3.00–6.00) | 4.00 (3.00–6.00) | 5.00 (4.00–6.50) | 5.00 (3.00–7.00) | 5.00 (3.00–7.00) | 4.50 (2.50–5.50) |
| Range | 0.00–9.00 | 0.00–8.00 | 0.00–8.00 | 0.00–8.00 | 0.00–9.00 | 0.00–9.00 | 0.00–9.00 |
| Age at administration, n (%) | |||||||
| 0 | 47 (33) | 15 (45) | 32 (30) | ||||
| 1 | 15 (11) | 3 (9.1) | 12 (11) | ||||
| 2 | 17 (12) | 4 (12) | 13 (12) | ||||
| 3 | 16 (11) | 2 (6.1) | 14 (13) | ||||
| 4 | 26 (18) | 4 (12) | 22 (20) | ||||
| 5 | 13 (9.2) | 5 (15) | 8 (7.4) | ||||
| 6 | 7 (5.0) | 7 (6.5) | |||||
| Not administered | 19 | ||||||
| Eligible infants for preventive program, n (%) | |||||||
| Catch-up | 128 (80) | 37 (84) | 27 (82) | 10 (91) | 91 (78) | 85 (79) | 6 (75) |
| Seasonal | 32 (20) | 7 (16) | 6 (18) | 1 (9.1) | 25 (22) | 23 (21) | 2 (25) |
| Preschool siblings | 44 (28) | 14 (32) | 9 (27) | 5 (45) | 30 (26) | 30 (28) | 0 (0) |
| Daycare | 12 (7.5) | 1 (2.3) | 1 (3.0) | 0 (0) | 11 (9.5) | 9 (8.3) | 2 (25) |
| Preterm | 18 (11) | 3 (6.8) | 2 (6.1) | 1 (9.1) | 15 (13) | 14 (13) | 1 (13) |
IQR, interquartile range; PC, primary care; RSV, respiratory syncytial virus; RT-PCR, real-time reverse-transcription polymerase chain reaction; SD, standard deviation.
Overall, 141 infants (88%) received nirsevimab, with 29 (21% of the sample) administered in-hospital during the RSV season, and 112 (79%) through the catch-up group.
Among the infants with LRTI, 44 (27.5%) tested positive for RSV, whereas 116 served as controls. Both groups exhibited similar age distributions, with 34% of cases and 33% of controls falling into the 0–3 months age range.
The onset of RSV cases was first observed in week 47, with 75% (31/44) concentrated between weeks 50/2023 and 2/2024 (Figure 1).
Weekly counts of LRTIs attended in primary care, testing positive (RSV+) and negative (RSV−) for RSV.
Weekly counts of LRTIs attended in primary care, testing positive (RSV+) and negative (RSV−) for RSV.
Among the cases, 33 (75%) had been immunized, as had 108 (93%) of the controls.
Seven children were later hospitalized, 3 of whom were aged at least 3 months. Of these children, 3 tested positive for RSV and were aged younger than 3 months old, 2 of them had been immunized, as 1 in the control group. The overall adjusted effectiveness of nirsevimab was 75.8% (95% CI: 40.4–92.7), and 80.2% (95% CI: 44.3–95.4) in the catch-up group (Figure 2).
Weekly counts of LRTIs attended in primary care, testing positive (RSV+) and negative (RSV−) for RSV.
Weekly counts of LRTIs attended in primary care, testing positive (RSV+) and negative (RSV−) for RSV.
Discussion
This study, conducted at PC centers, demonstrated that nirsevimab was 76% effective in preventing medically attended RSV-LRTI in infants aged younger than 10 months old. This finding aligns with the 79.5% efficacy observed in clinical trials against medically attended RSV-LRTI cases.15 Most of the studies of RSV epidemiology in young children have been performed in hospitalizations.1–3 In epidemiological studies of bronchiolitis, although the peak of hospitalizations occurs in the first 2 months of life, the highest incidence in PC occurs between 5 and 7 months of age,4 which explains that 67% of the cases in this study were aged older than 3 months, and in hospitalized cases17 most children were aged between 0 and 3 months. So, 82% of the infants included in this study were born out of season and had received nirsevimab as a catch-up. As the effectiveness to prevent RSV-LRTI in these infants was 80.2%, we can affirm that the catch-up has demonstrated a greater effectiveness in preventing cases compared with the seasonal program. Therefore, this underscores the importance of implementing a catch-up program to prevent RSV in older infants.
An increasing number of studies are being published to assess the effectiveness and impact of nirsevimab in preventing hospitalizations.17–20,24 In general, good protection is shown, with some variability in the figures, because of the study designs and the uptake. However, to assess how this product performs in outpatient settings is also important, not only because its high frequency of presentation, but also to acknowledge the potential long-term benefit if the infection in the first years of life is a driver of chronic conditions as asthma or chronic obstructive pulmonary disease in later life.6,9,10
The main strengths of this study are its extensive network of PC centers and the use of the TND, a widely recognized and efficient method for estimating the effectiveness of immunization strategies.25 The TND allows to perform the study even if not all cases of LRTI were collected. A selection bias could occur in this instance, but the fact that the proportion of RSV cases in nonimmunized patients (58%) is similar with previously published data26 decreases its possibility. It is important to acknowledge the importance of clinical practice variability, especially when many practices are included in the study. We have previously shown a large practice variability in the hospitalization of RSV-LRTI17 and all-cause bronchiolitis.4 Lack of control of the variability may under or overestimate the effectiveness of the intervention. To account for this variability, the different socioeconomic situation of the PC centers and their demographic differences, that result in unexplained differences, PC center was included in the model as a random effect.
The major limitation of this study is the low precision of the results, shown by the wide CIs. Setting up a PC research network of this size is difficult. As the PCR identification of RSV in PC is not routinely performed, other epidemiological designs, as a cohort study, would have failed to assess the incidence of the disease, and therefore the effectiveness. Moreover, the sample size was insufficient to assess the effectiveness by disease severity, although it was not one of the initial objectives of this study.
Conclusion
Our results underscore the effectiveness of nirsevimab in preventing medically attended LRTI in infants in outpatient settings and emphasize the importance of a catch-up immunization program to reduce the disease burden in PC.
Ms López-Lacort conceptualized and designed the study, contributed to data acquisition and interpretation, performed the analysis, drafted, cross-reviewed the manuscript, and approved the final version. Drs Muñoz-Quiles, Mira-Iglesias, Díez-Domingo, and Orrico-Sánchez conceptualized and designed the study, contributed to data acquisition and interpretation, drafted, cross-reviewed the manuscript, and approved the final version. Dr López-Labrador contributed to data acquisition and interpretation, cross-reviewed the manuscript, and approved the final version. Dr Garcés-Sánchez, Ms Escribano-López, Dr Zornoza-Moreno, Dr Pérez-Martín, Dr Alfayate-Miguelez, Dr Iofrío-De Arce, Dr Pastor-Villalba, and Dr Lluch-Rodrigo participated in data acquisition, cross-reviewed the manuscript, and approved the final version. Furthermore, all authors have collectively agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
CONFLICT OF INTEREST DISCLOSURES: Dr Muñoz-Quiles, Ms López-Lacort, Dr Díez-Domingo, and Dr Orrico-Sánchez have attended several congresses, whose registration, travel, and accommodation costs were covered by MSD, GSK, AZ, and SP. Drs Orrico-Sánchez and Díez-Domingo, along with their institution, have received research grants from SP, GSK, and AZ for studies unrelated to this one. Drs Orrico-Sánchez and Díez-Domingo have acted as advisors for this immunization strategy to SP, with Dr Orrico-Sánchez also advising Moderna. Dr Mira-Iglesias has received fees for conferences/experts’ meetings from SP and for educational events from MSD. Dr López-Labrador has received funding from SP and Merck for studies unrelated to this one. Dr Iofrío-De Arce has collaborated in educational activities supported by AZ, GSK, MSD, and Pfizer, and as a consultant on the Advisory Board of GSK and Pfizer. He has received support from GSK, MSD, and Pfizer to attend national educational activities. Dr Zornoza-Moreno has collaborated in teaching activities funded by AZ, GSK, and MSD, and as a consultant on the Advisory Board of MSD. She has received support from GSK, Seqirus, AZ, MSD, and Pfizer to attend national and international teaching activities. Dr Garcés-Sánchez has received honoraria from GSK group of companies, Pfizer, Sanofi, and MSD, for taking part in advisory boards and experts’ meetings and for acting as a speaker in congresses outside the scope of the submitted work. Dr Pérez-Martín has received support for teaching activities from AZ, GSK, Pfizer, and MSD, and as a consultant on the Advisory Board of MSD, Sanofi, and Moderna. He has received support from GSK, Seqirus, AZ, GSK, MSD, and Pfizer to attend national and international teaching activities. Dr Alfayate-Miguelez has received support to attend teaching activities from Pfizer and MSD. Dr Pastor-Villalba has collaborated in educational activities whose registration, travel, and accommodation costs were covered by GSK, Seqirus, AZ, MSD, and Pfizer. Other authors declare no conflict of interest.
FUNDING: This work is, in part, funded by the Instituto de Salud Carlos III from the European funds of the Recovery, Transformation, and Resilience Plan, with file code CD22/00122, by virtue of the Resolution of the Directorate of the Instituto de Salud Carlos III, O.A., M.P. of December 14, 2022, awarding the Sara Borrell Contracts of the 2022 call of the Strategic Action in Health 2021–2023. This work is also funded by the European Union – NextGenerationEU; The (partial) funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Acknowledgments
Members of the MEDIPRIM network include: Beatriz Mengual-Chuliá, Ángel Valls Arévalo, Ignacio Sorribes Monrabal, Luis Blesa, Isabel Úbeda Sansano, Juan Carlos Julia Benito, Martin Rodenas, Julia Fujkova, Marcos Romero García, Antonio Garcia Garcia, Virginia Jarabo Garín, Gema María Sevilla Guerra, Ana Fullana Montoro, Cristina Ortolá Feliu, Teresa Alcayte Blat, Eva Huerta, Julia Ruiz Jiménez, Nacho Domingo, Mireia Ariño i Torregrosa, Paula Rodríguez-Cantón, Catalina Sánchez Medina, Lara García Almiñana, Ana Belén Ferrer Bautista, Elena Martínez Chillarón, Elvira Muñoz Vicente, Trinidad Álvarez de Laviada, Leyre Martí Martí, Silvia Sánchez Precioso, María Victoria González Cortés, Carolina Torres Chazarra, Ana Montañés, Esther Pitarch, María José Palomares, Almudena Navarro Ruiz, Sergii Semchenko, Mayte Escobar, Joaquín Roig, Mari Carmen López, Mireia Ricart, Irene Satorre, Inma Ortells Ramón, Olga Peñalver Giner, María Martínez Pastor, Rebeca Pérez Ferrando, Esther Mazón Ruiz, Natalia Verdú Díaz, Ángeles Betiana Maurizi, Lucía González-Moro, Ana Palmero Miralles, María Nadia Sayed Sancho, María del Carmen Pérez Pérez, Violeta Olivares Ferrándiz, Bernardo Cervantes Martínez, David Zapata Hernández, Sonia Patricia Molina López, Marta Díaz Ruiz, Estefanía Aguilar Ros, María Fuensanta Alemán Lorca, Juan Francisco Soriano Ibarra, Dánae Cuadrado García, Miriam Lorente Cuadrado, Elena Isabel Martínez Martínez, Nelson Paul Contreras Corletto, Salvador Gil Sánchez, Sonia Herreros Juárez, Juan José Vigueras Abellán, María Pilar Talón Moreno, María Pilar Barceló Martínez, María José Vicente Fernández, María Vizcaíno Monedero, Elisabeth Cava Almohalla, Luisa María García Sandoval, Santa Elisabeth Marcano, Silvia Martínez García, Isabel Moya Cossío, María Herráiz Martínez, Joaquín López Alcaraz, María José Olmos Jiménez, Gonzalo Ramón Sanz Mateo, María Dolores Carrillo Vinader, Jesús Enrique Meca Garrido, Inés Ángeles Machado Mudarra, María Lucía García Mancebo, Antonio Jesús Castellanos Alcarria, Jaume Enjuanes Llovet, Tania Doris Amaguaña Alverca, María Victoria López Robles, Laura Úbeda Cuenca, Ygnacia Clase Toribio, María José Ruiz Ríos, Enid Iberka Terrero Dajer. We also wish to acknowledge the Fundación para la Formación e Investigaciones Sanitarias de la Región de Murcia (FFIS) and the Instituto Murciano de Investigación Biomédica (IMIB) for their efforts and bureaucratic assistance in making it possible to carry out the study in the Region of Murcia, and Yolanda García Gambín, Laura Moreno Parrado and Marina Simón Páez of the Microbiology Service of the Hospital Clínico Universitario Virgen de la Arrixaca.
Comments
Methodological Considerations in Calculating the Effectiveness of Nirsevimab: A Statistical Perspective
While acknowledging the undoubted significance of nirsevimab as a potential game-changer in RSV prevention among young infants, we would like to raise some methodological considerations regarding the statistical analysis. The authors calculated effectiveness using the formula (1 - Odds Ratio (OR)) × 100%, where the OR represents the odds of testing positive for RSV given nirsevimab administration compared to the odds without nirsevimab. Our independent statistical analysis, employing conventional methodological approaches to the data presented in Table 1 and Figure 2, yielded effectiveness rates of 59.6% (95% confidence interval: 32.8-86.4) and 61.4% (95% confidence interval: 35.2-87.6), respectively. To ensure methodological rigor, we conducted additional analyses utilizing Bayesian logistic regression, which demonstrated effectiveness rates of 57.8% (95% CI: 29.5-84.2) for the overall cohort and 59.8% (95% CI: 31.5-85.9) for the catch-up cohort. The observed differential of approximately 15 percentage points between our findings and the reported results merits further examination. This variance may be attributed to several methodological considerations and prior distribution assumptions in the statistical modeling, which we believe warrant detailed elucidation to enhance the robustness of the effectiveness estimates. The study's multi-center design, encompassing 57 primary care centers across two Spanish regions, and the predominant recruitment from catch-up programs introduce complexity to the statistical analysis. Bayesian regression methods are particularly valuable in such contexts, especially when dealing with small sample sizes, multi-center studies, and potentially imbalanced data distributions.3 These methodological considerations do not diminish the evident efficacy of nirsevimab as a monoclonal antibody intervention.4, 5 Rather, we believe that additional clarification of the statistical methodology would enhance our understanding of nirsevimab's therapeutic benefits and provide valuable insights for future research and clinical applications.
We would greatly appreciate the authors' perspective on these statistical considerations, as their insights would contribute to a more comprehensive understanding of nirsevimab's effectiveness in real-world settings.
Sincerely,
Hsin Chi, Li-Min Huang, Chien-Yu Lin*
National Taiwan University Children’s Hospital, Taipei city; Hsinchu Municipal MacKay Children’s Hospital, Hsinchu city, Taiwan
*Corresponding author: [email protected]
References:
1. Wilkins D, Wählby Hamrén U, Chang Y, Clegg LE, Domachowske J, Englund JA, et al. RSV Neutralizing Antibodies Following Nirsevimab and Palivizumab Dosing. Pediatrics. 2024;154(5):e2024067174
2. López-Lacort M, Muñoz-Quiles C, Mira-Iglesias A, López-Labrador FX, Garcés-Sánchez M, Escribano-López B, et al. Nirsevimab Effectiveness Against Severe RSV Infection in the Primary Care Setting. Pediatrics. 2024. Doi: 10.1542/peds.2024-066393
3. Goligher EC, Heath A, Harhay MO. Bayesian statistics for clinical research. Lancet. 2024;404(10457):1067-1076
4. Andina Martínez D, Claret Teruel G, Gijón Mediavilla M, Cámara Otegui A, Baños López L, de Miguel Lavisier B, et al. Nirsevimab and Acute Bronchiolitis Episodes in Pediatric Emergency Departments. Pediatrics. 2024;154(4):e2024066584
5. Domachowske J, Hamrén UW, Banu I, Baronio R, Basavaraju B, Koen A, et al. Safety and Pharmacokinetics of Nirsevimab in Immunocompromised Children. Pediatrics. 2024;154(4):e2024066508