Introducción: Recientemente se ha aprobado en Europa y en España el uso de nirsevimab, un anticuerpo monoclonal (AcM) para la prevención de la enfermedad por virus respiratorio sincitial (VRS). Objetivos: Facilitar unas recomendaciones para la administración de nirsevimab para la prevención de la enfermedad por VRS. Métodos: Para la elaboración de estas recomendaciones, se decidió realizar una revisión crítica de la literatura, utilizando la metodología Delphi y la metodología GRADE. Se definió un grupo de expertos. Se realizaron tres rondas para definir las preguntas, manifestarse a favor o en contra, graduar la recomendación, y definir el acuerdo o el desacuerdo con las conclusiones. Resultados: En la población general de recién nacidos, se recomienda administrar rutinariamente nirsevimab para reducir la enfermedad y la hospitalización por bronquiolitis y enfermedad de vías bajas por VRS. Se recomienda administrar nirsevimab a todos los lactantes que nazcan en la estación de alta incidencia de VRS y aquellos que cuando esta comience, tengan menos de seis meses de edad. En los pacientes prematuros de 29 a 35 semanas de edad gestacional, en los lactantes con cardiopatía hemodinámicamente significativa y lactantes con enfermedad pulmonar crónica se recomienda rutinariamente administrar nirsevimab para reducir la enfermedad y la hospitalización por bronquiolitis y enfermedad de vías bajas por VRS. En los pacientes con indicación actual de palivizumab, se recomienda sustituir palivizumab por nirsevimab para reducir la carga de enfermedad de bronquiolitis. Conclusiones: Se recomienda administrar rutinariamente nirsevimab a todos los recién nacidos menores de seis meses nacidos en la estación de VRS o que tengan menos de seis meses cuando entran en la estación invernal, para reducir la carga de enfermedad y la hospitalización por bronquiolitis. (AU)

BACKGROUND: The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear. METHODS: In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen. RESULTS: A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P = 0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group. CONCLUSIONS: Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) among infants and young children, resulting in annual epidemics in Japan. Children with congenital or acquired immunodeficiencies, transplant recipients, and those receiving immunosuppressive therapy are at increased risk for severe RSV-associated LRTI with prolonged viral shedding and higher viral loads, resulting in prolonged hospitalizations, admissions to the intensive care unit (ICU), and the need for mechanical ventilation. Palivizumab (Synagis®) is the only approved agent for RSV prophylaxis, and its half-life (t1/2) is approximately 1 month, infants and young children need to receive monthly intramuscular doses of palivizumab throughout the RSV season to maintain protection. This constitutes a significant burden on healthcare providers as well as the infants/children and their families. Nirsevimab may provide a cost-effective opportunity to protect all infants from RSV disease based on an improvement in potency and the extended t1/2 that is expected to support once-per-RSV-season dosing.

Respiratory tract infections caused by respiratory syncytial virus (RSV) are a worldwide burden and represent a major public health issue. In France, bronchiolitis is responsible for around 100,000 emergency room visits and 50,000 hospital admissions every year; 75% of infants hospitalised for RSV bronchiolitis are healthy full-term children. Recent discoveries concerning the specific viral epitopes of RSV have made it possible to move from an empirical approach to a targeted preventive or curative approach (monoclonal antibodies, vaccines, anti-viral drugs). Nirsevimab is a monoclonal antibody against RSV with enhanced neutralising activity and a prolonged half-life. A randomised, placebo-controlled phase III trial demonstrated the effectiveness of nirsevimab in reducing lower respiratory tract infections caused by RSV requiring medical management in healthy premature and term infants, with a favourable safety profile. The US Food and Drug Administration (FDA) approved the first RSV vaccine on May 3, 2023, and the second was approved on May 31, 2023. Nirsevimab was approved by the European Medicines Agency (EMA) on November 4, 2022.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose. METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose. RESULTS: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions. CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).

The purpose of this study is to evaluate the impact of nirsevimab in preventing RSV in healthy infants and high-risk children less than 24 months of age at the start of RSV season in Galicia. The target population to receive nirsevimab is around 14,000 subjects including all healthy newborns during the RSV season, those \< 6 months at the start of the season, as well as those \< 24 months with comorbidities at the start of the season. Nirsevimab will be administered as part of the immunization program of Galicia and following the implementation plan designed by the Public Health authorities, using the vaccination facilities of the Galician system, i.e., hospitals and primary care centres. Appointments for administration and registration of administered doses will be performed as per usual immunization protocols. The expected coverage with nirsevimab in the target population is expected to be high (\>80%). RSV testing is routinely performed in the hospital and emergency department settings. The Galician Regional Surveillance Information System will retrieve all the existing information of the different electronic databases for new RSV cases detected in Galicia, including hospitalization, primary care, drug administration and immunization. RSV case ascertainment and classification will be per- formed by a specialized clinical team according to pre-established definitions.

Bronchiolitis is a very common viral lower respiratory tract infection in infants that consists of swelling of the small airway passages in the lungs. Signs and symptoms typically begin with rhinitis and cough, which may progress to tachypnea, wheezing, rales, use of accessory muscles, and/or nasal flaring. The most common etiology of bronchiolitis is respiratory syncytial virus (RSV), with the highest incidence of infection occurring between October and March in the Northern Hemisphere. RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year. Premature infants, and those with chronic lung disease of prematurity or significant congenital heart disease, are at highest risk for severe RSV disease. Approximately 1% to 3% of children under 12 months of age in the United States are hospitalized each year due to RSV, according to the American Academy of Pediatrics. Similar figures are found in other countries. Despite the huge burden that RSV infections represents in infants, no specific effective treatment, nor an efficacious prevention strategy had been available for term and healthy infants. The only FDA-approved product to prevent severe RSV disease among infants and young children was palivizumab, a monoclonal antibody. However, the American Academy of Pediatrics (AAP) recommends palivizumab only for children with certain underlying medical conditions (comprising \<5% of all infants). In July 2023, the Food and Drug Administration approved nirsevimab (Beyfortus®), a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Beyfortus® is indicated for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. In Europe, The European Medicines Agency approved the use of BEYFORTUS in October 2022. In France, The Haute Autorité de Santé (HAS) approved the use of BEYFORTUS in July 2023 starting in September 2023. Beyfortus is administered as a single intramuscular injection prior to or during RSV season. This single dose may provide protection during the whole RSV season. The safety and efficacy of Beyfortus® were supported by three clinical trials (1-3). The key measure of efficacy was the incidence of medically attended RSV lower respiratory tract infection (MA RSV LRTI ) evaluated during the 150 days after Beyfortus® administration. One trial included 1,453 preterm infants (born at greater than or equal to 29 weeks of gestational age up to less than 35 weeks of gestation) who were born during or entering their first RSV season (1). Of the 1,453 preterm infants in the trial, 969 received a single dose of Beyfortus® and 484 received placebo. Among infants who were treated with Beyfortus®, 25 (2.6%) experienced MA RSV LRTI compared with 46 (9.5%) infants who received placebo. Beyfortus® reduced the risk of MA RSV LRTI by approximately 70% relative to placebo. A second trial included 1,490 term and late preterm infants (born at greater than or equal to 35 weeks in gestational age), 994 of whom received a single dose of Beyfortus® and 496 of whom received placebo (2). Among infants who were treated with Beyfortus®, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo. Beyfortus® reduced the risk of MA RSV LRTI by approximately 75% relative to placebo. In a third randomized, double-blind, controlled trial assessing the safety of nirsevimab for RSV in infants with heart or lung disease or prematurity, authors reported that the safety profile of nirsevimab was similar to that of palivizumab. Objective The objective of this observational study is to assess in the real-world the effectiveness of nirsevimab on the Emergency Department use for bronchiolitis as well on the effectiveness of nirsevimab to reduce hospitalization and healthcare usage in France where a national campaign to administer nirsevimab to young infants stated on September 14th, 2023. Type of study Retrospective observational study of medical records which include systematic and prospective data on nirsevimab immunization status of patients visiting the Emergency Department. Methodology This retrospective observational study will include two data set analysis. On one part, data from all infants presenting to the emergency department and diagnosed as having bronchiolitis will be retrieved from medical and nursing records and those who had been given nirsevimab will be compared with those who did not receive this medication prior to the ED visit. On the other part, since the investigators have included nirsevimab administration in our systematic data collection on immunization of all infants visiting our ED, they will use the nirsevimab immunization status of infants diagnosed as having bronchiolitis with those do not having bronchiolitis in order to assess the effectiveness (real-world effect) of nirsevimab on the ED use and hospitalization. The investigators included in the medical and nursing records of all patients with bronchiolitis data on the previous administration of nirsevimab on Octobre 14th, 2023. They also included on October 31st, 2023 in the medical and nursing records of all children younger than 13 months visiting the ED the nirsevimab administration whatever the reason of ED visit was. Sample calculation The investigators used the primary objective, measurement of the real-world nirsevimab effectiveness to reduce pediatric emergency department use (PED), as a target to calculate our sample population. They computed the number of subjects needed by setting the lower boundary of the effectiveness confidence interval at 20% in infants aged 0 to 6 months. They assumed a 20% incidence of bronchiolitis in infants up to one year of age visiting the PED over the bronchiolitis season, a 50% effectiveness of Beyfortus® to reduce PED use for bronchiolitis, and a 30% rate of Beyfortus® administration in the 0-6 months population. The investigators computed the variance of the screening method estimator using the delta method. With the aforementioned hypotheses, the investigators found that a minimum of 500 infants up to one year of age will be needed. Since approximately 100 infants aged 0 to 6 months visit this PED every week during the bronchiolitis season, the investigators expect to collect the needed sample using visits from October to December.

RSV, the leading cause of bronchiolitis, primarily affects young children. According to the Centers for Disease Control and Prevention (CDC), RSV accounts for an annual 2.1 million outpatient visits, 58,000-80,000 hospitalizations, and 100-300 deaths in children <5 years old.1 Infants <6 months of age are at greatest risk of hospitalization, with the highest morbidity and costs in infants born prematurely.2,3 In addition, RSV infections lead to economic productivity loss and heightened parental emotional stress.4 Along with Coronavirus Disease 2019 (COVID-19) and influenza, respiratory season can significantly strain the healthcare system, as was seen and experienced by many pediatric hospitalists during the 2022-2023 "tripledemic."

OBJECTIVE: Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. DATA SOURCES: A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. DATA SYNTHESIS: Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING AGENTS: Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. CONCLUSIONS: Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, -8.6 to 86.8; P = 0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).