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Human Vaccines & Immunotherapeutics Aug 2023Palivizumab has been shown to decrease RSV-related hospitalization (RSVH) risk and reduce RSVH severity. American Academy of Pediatrics (AAP) guidance on administration...
Palivizumab has been shown to decrease RSV-related hospitalization (RSVH) risk and reduce RSVH severity. American Academy of Pediatrics (AAP) guidance on administration of palivizumab has changed over time; in 2014, palivizumab was no longer recommended in preterm infants born at 29 weeks gestational age (wGA) or later. This study's objective was to describe RSVH risk and severity in preterm infants (29-34 wGA) without comorbidities relative to healthy term infants and to each other by gestational age. Using the MarketScan Multi-State Medicaid and Commercial Databases, infants born from July 1, 2014 to June 30, 2019, at 29-34 wGA (preterm) and >37 wGA (term) were identified. During RSV seasons (November to March) from 2014 to 2020, claims incurred by infants while they were <6 months old were evaluated for RSVH and RSVH characteristics. This study included 63,351 preterm infants and 1,076,389 term infants without outpatient palivizumab administration. Rate of RSVH was higher in infants with lower wGA at birth and ranged 3.32-5.72 per 100 infant-seasons in Medicaid-insured infants and 3.21-4.84 in commercially insured infants. Relative risk of RSVH was 5-8 times higher in Medicaid-insured preterm infants and 3-5 times higher in commercially insured preterm infants compared to term infants. ICU admissions and mechanical ventilation were more common during RSVH in preterm infants relative to term infants. RSV-related outpatient healthcare utilization was also 2-3 times higher in preterm infants born at 31-34 wGA. Increased utilization of palivizumab among infants born at 29-34 wGA may decrease RSVH rates and result in less severe course in preterm infants with RSVH.
Topics: Infant; Infant, Newborn; Humans; Child; United States; Palivizumab; Gestational Age; Infant, Premature; Antiviral Agents; Outpatients; Respiratory Syncytial Virus Infections; Hospitalization
PubMed: 37828711
DOI: 10.1080/21645515.2023.2252289 -
American Journal of Perinatology May 2024Palivizumab is a humanized monoclonal antibody approved for the prevention of serious lower respiratory tract infection (LRTI) caused by respiratory syncytial virus...
OBJECTIVE
Palivizumab is a humanized monoclonal antibody approved for the prevention of serious lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) in infants and young children at high risk of RSV disease. This systematic review summarized evidence on the effectiveness and safety of palivizumab when used in approved populations.
STUDY DESIGN
A systematic review of Phase III trials and observational studies was conducted according to the population, intervention, comparator, outcome, timing, setting (PICOTS) approach (PROSPERO, CRD42021281380). Target populations consisted of infants with a history of premature birth (≤35-week gestational age) and children aged <2 years with bronchopulmonary dysplasia (BPD) or with hemodynamically significant congenital heart disease (hs-CHD). Outcomes of interest included RSV-related hospitalization, admission to intensive care unit (ICU), requirement for mechanical ventilation, treatment-related adverse events (AEs), and RSV-related deaths. Information sources were literature search (Ovid MEDLINE and Embase), pragmatic searches, and snowballing (covering the period up to 07 September 2021).
RESULTS
A total of 60 sources were included (5 Phase III trials and 55 observational studies). RSV-related hospitalization rates following palivizumab prophylaxis in Phase III trials were 1.8% in premature infants and 7.9% in children with BPD, which were significantly lower than rates in placebo arms. In the real-world setting, similar hospitalization rates were found (0.7-4.0% in premature infants [16 studies] and 0-5.5% in patients with BPD [10 studies]) with ICU admission reported in 0 to 33.3% of patients hospitalized for RSV. In Phase III trials, RSV-related mortality rates were 0.2 and 0.3%, while AEs occurred in 11% of premature and/or BPD patients and 7.2% of hs-CHD patients, consisting mainly of injection site reaction, fever, and diarrhea. Similar results were found in observational studies.
CONCLUSION
This systematic review supports the effectiveness and safety of palivizumab in the indicated populations.
KEY POINTS
· Systematic review supports the positive benefit-risk profile of palivizumab in the indicated populations.. · Real-world safety and effectiveness of palivizumab are consistent with Phase III trials results.. · Palivizumab reduces RSV-related hospitalizations, ICU admissions, and need for mechanical ventilation..
Topics: Humans; Palivizumab; Respiratory Syncytial Virus Infections; Antiviral Agents; Infant; Infant, Newborn; Infant, Premature; Hospitalization; Bronchopulmonary Dysplasia; Heart Defects, Congenital; Respiration, Artificial; Respiratory Tract Infections; Observational Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 36452969
DOI: 10.1055/a-1990-2633 -
Nature Communications Apr 2024Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants....
Currently, only Palivizumab and Nirsevimab that target the respiratory syncytical virus (RSV) fusion protein are licensed for pre-treatment of infants. Glycoprotein-targeting antibodies may also provide protection against RSV. In this study, we generate monoclonal antibodies from mice immunized with G proteins from RSV-A2 and RSV-B1 strains. These monoclonal antibodies recognize six unique antigenic classes (G0-G5). None of the anti-G monoclonal antibodies neutralize RSV-A2 or RSV-B1 in vitro. In mice challenged with either RSV-A2 line 19 F or RSV-B1, one day after treatment with anti-G monoclonal antibodies, all monoclonal antibodies reduce lung pathology and significantly reduce lung infectious viral titers by more than 2 logs on day 5 post-RSV challenge. RSV dissemination in the lungs was variable and correlated with lung pathology. We demonstrate new cross-protective anti-G monoclonal antibodies targeting multiple sites including conformation-dependent class G0 MAb 77D2, CCD-specific class G1 MAb 40D8, and carboxy terminus of CCD class G5 MAb 7H11, to support development of G-targeting monoclonal antibodies against RSV.
Topics: Humans; Mice; Animals; Antibodies, Monoclonal; Respiratory Syncytial Virus Infections; Antibodies, Viral; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; GTP-Binding Proteins; Respiratory Syncytial Virus Vaccines; Antibodies, Neutralizing
PubMed: 38575575
DOI: 10.1038/s41467-024-47146-2 -
Viruses Nov 2023(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to...
(1) Background: Palivizumab has been an approved preventative monoclonal antibody for respiratory syncytial virus (RSV) infection for over two decades. However, due to its high cost and requirement for multiple intramuscular injections, its use has been limited mostly to high-income countries. Following our previous study showing the successful lung deposition of aerosolised palivizumab in lambs, this current study evaluated the "proof-of-principle" effect of aerosolised palivizumab delivered as a therapeutic to neonatal lambs following RSV infection. (2) Methods: Neonatal lambs were intranasally inoculated with RSV-A2 on day 0 (day 3 post-birth) and treated with aerosolised palivizumab 3 days later (day 3 post-inoculation). Clinical symptoms, RSV viral load and inflammatory response were measured post-inoculation. (3) Results: Aerosolised therapeutic delivery of palivizumab did not reduce RSV viral loads in the nasopharynx nor the bronchoalveolar lavage fluid, but resulted in a modest reduction in inflammatory response at day 6 post-inoculation compared with untreated lambs. (4) Conclusions: This proof-of-principle study shows some evidence of aerosolised palivizumab reducing RSV inflammation, but further studies using optimized protocols are needed in order to validate these findings.
Topics: Animals; Sheep; Palivizumab; Respiratory Syncytial Virus Infections; Antiviral Agents; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human
PubMed: 38005952
DOI: 10.3390/v15112276 -
Paediatric Drugs Mar 2024Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, and is associated with long-term pulmonary sequelae...
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, and is associated with long-term pulmonary sequelae for up to 30 years after infection. The mainstay of RSV management is supportive therapy such as supplemental oxygen. Palivizumab (Synagis™-AstraZeneca), a monoclonal antibody targeting the RSV F protein site II, has been licensed for the prevention of RSV in high-risk groups since 1998. There has been recent promising progress in preventative strategies that include vaccines and long-acting, high-potency monoclonal antibodies. Nirsevimab (Beyfortus™-AstraZeneca/Sanofi), a monoclonal antibody with an extended half-life, has recently been registered in the European Union and granted licensure by the US Food and Drug Administration. Furthermore, a pre-fusion sub-unit protein vaccine has been granted licensure for pregnant women, aimed at protecting their young infants, following established safety and efficacy in clinical trials (Abrysvo™-Pfizer). Also, multiple novel antiviral therapeutic options are in early phase clinical trials. The next few years have the potential to change the landscape of LRTI through improvements in the prevention and management of RSV LRTI. Here, we discuss these new approaches, current research, and clinical trials in novel therapeutics, monoclonal antibodies, and vaccines against RSV infection in infants and children.
Topics: Pregnancy; United States; Child; Infant; Female; Humans; Respiratory Syncytial Virus Infections; Palivizumab; Antibodies, Monoclonal; European Union; Vaccines
PubMed: 38032456
DOI: 10.1007/s40272-023-00606-6 -
Journal of the Association of Medical... Nov 2023The introduction of nirsevimab (a respiratory syncytial virus [RSV] monoclonal antibody that can protect for minimum 5 months with a single dose) and RSV maternal...
The introduction of nirsevimab (a respiratory syncytial virus [RSV] monoclonal antibody that can protect for minimum 5 months with a single dose) and RSV maternal vaccines to protect young infants has the potential to dramatically decrease RSV hospitalizations in Canada. However, there remain many unanswered questions before optimal use of these products can be assured.
PubMed: 38058503
DOI: 10.3138/jammi-2023-05-31 -
Italian Journal of Pediatrics Mar 2024Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD)...
BACKGROUND
Respiratory Syncytial Virus (RSV) infections may lead to severe consequences in infants born preterm with breathing problems (such as bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS)) or congenital heart diseases (CHD). Since studies investigating the influence of different gestational age (WGA) and concomitant specific comorbidities on the burden of RSV infections are scarce, the present study aimed to better characterize these high-risk populations in the Italian context.
METHODS
This retrospective, longitudinal and record-linkage cohort study involved infants born between 2017 and 2019 in Lazio Region (Italy) and is based on data extracted from administrative databases. Each infant was exclusively included in one of the following cohorts: (1) BPD-RDS (WGA ≤35 with or without CHD) or (2) CHD (without BPD and/or RDS) or (3) Preterm (WGA ≤35 without BPD (and/or RDS) or CHD). Each cohort was followed for 12 months from birth. Information related to sociodemographic at birth, and RSV and Undetermined Respiratory Agents (URA) hospitalizations and drug consumption at follow-up were retrieved and described.
RESULTS
A total of 8,196 infants were selected and classified as 1,084 BPD-RDS, 3,286 CHD and 3,826 Preterm. More than 30% of the BPD-RDS cohort was composed by early preterm infants (WGA ≤ 29) in contrast to the Preterm cohort predominantly constitute by moderate preterm infants (98.2%), while CHD infants were primarily born at term (83.9%). At follow-up, despite the cohorts showed similar proportions of RSV hospitalizations, in BPD-RDS cohort hospitalizations were more frequently severe compared to those occurred in the Preterm cohort (p<0.01), in the BPD-RDS cohort was also found the highest proportion of URA hospitalizations (p<0.0001). In addition, BPD-RDS infants, compared to those of the remaining cohorts, received more frequently prophylaxis with palivizumab (p<0.0001) and were more frequently treated with adrenergics inhalants, and glucocorticoids for systemic use.
CONCLUSIONS
The assessment of the study clinical outcomes highlighted that, the demographic and clinical characteristics at birth of the study cohorts influence their level of vulnerability to RSV and URA infections. As such, continuous monitoring of these populations is necessary in order to ensure a timely organization of health care system able to respond to their needs in the future.
Topics: Infant; Infant, Newborn; Humans; Respiratory Syncytial Virus Infections; Infant, Premature; Retrospective Studies; Cohort Studies; Palivizumab; Hospitalization; Heart Defects, Congenital; Bronchopulmonary Dysplasia; Antiviral Agents
PubMed: 38528568
DOI: 10.1186/s13052-024-01627-8 -
BMC Infectious Diseases Apr 2024Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of...
AIM
Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations.
METHODS
We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses.
RESULTS
Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results.
CONCLUSION
Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.
Topics: Infant; Infant, Newborn; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Colombia; Antiviral Agents; Infant, Premature; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human; Heart Defects, Congenital; Hospitalization
PubMed: 38641577
DOI: 10.1186/s12879-024-09300-5 -
European Journal of Pediatrics Jun 2024We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and... (Observational Study)
Observational Study
UNLABELLED
We aimed to describe differences in the epidemiology, management, and outcomes existing between centers located in countries which differ by geographical location and economic status during to post-pandemic bronchiolitis seasons. This was a prospective observational cohort study performed in two academic centers in Latin America (LA) and three in Italy. All consecutive children with a clinical diagnosis of bronchiolitis were included, following the same data collection form. Nine hundred forty-three patients have been enrolled: 275 from the two Latin American Centers (San Jose, 215; Buenos Aires, 60), and 668 from Italy (Rome, 178; Milano, 163; Bologna, 251; Catania, 76). Children in LA had more frequently comorbidities, and only rarely received palivizumab. A higher number of patients in LA had been hospitalized in a ward (64% versus 23.9%, p < 0.001) or in a PICU (16% versus 6.2%, p < 0.001), and children in LA required overall more often respiratory support, from low flow oxygen to invasive mechanical ventilation, except for CPAP which was more used in Italy. There was no significant difference in prescription rates for antibiotics, but a significantly higher number of patients treated with systemic steroids in Italy.
CONCLUSIONS
We found significant differences in the care for children with bronchiolitis in Italy and LA. Reasons behind such differences are unclear and would require further investigations to optimize and homogenize practice all over the world.
WHAT IS KNOWN
• Bronchiolitis is among the commest cause of morbidity and mortality in infants all over the world.
WHAT IS NEW
• There are significant differences on how clinicians care for bronchiolitis in different centers and continents. Differences in care can be principally due to different local practices than differences in patients severity/presentations. • Understanding these differences should be a priority to optime and standardize bronchiolitis care globally.
Topics: Humans; Italy; Prospective Studies; Infant; Male; Female; Bronchiolitis; Latin America; Infant, Newborn; Treatment Outcome; Hospitalization; Child, Preschool; Palivizumab
PubMed: 38554172
DOI: 10.1007/s00431-024-05530-6 -
Tropical Medicine and Infectious Disease Dec 2023Respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. Virus-specific monoclonal...
Respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. Virus-specific monoclonal antibodies (mAbs) can be used for diagnosis, prophylaxis, and research of RSV pathogenesis. A panel of 16 anti-RSV mAbs was obtained from mice immunized by RSV strain Long. Half of them had virus-neutralizing activity. According to Western blot all of these mAbs effectively bound native oligomeric (homodimeric and homotrimeric) forms of the RSV fusion (F) protein. Only five of the mAbs interacted with the monomeric form, and only one of these possessed neutralizing activity. None of these mAbs, nor the commercial humanized neutralizing mAb palivizumab, reacted with the denaturated F protein. Thus, interaction of all these mAbs with F protein had clear conformational dependence. Competitive ELISA and neutralization assays allowed the identification of nine antigenic target sites for the interaction of mAb with the F protein. Five partially overlapping sites may represent a complex spatial structure of one antigenic determinant, including one neutralizing and four non-neutralizing epitopes. Four sites (three neutralizing and one non-neutralizing) were found to be distinct. As a result of virus cultivation RSV-A, strain Long, in the presence of a large amount of one of the neutralizing mAbs, an escape mutant with a substitution, N240S, in the F protein, was obtained. Thus, it was shown for the first time that position 240 is critical for the protective effect of an anti-RSV antibody. To assess the ability of these mAbs to interact with modern RSV strains circulating in St. Petersburg (Russia) between 2014 and 2022, 73 RSV-A and 22 RSV-B isolates were analyzed. Six mAbs were directed to conserved epitopes of the F protein as they interacted most efficiently with both RSV subtypes in a fixed cell-ELISA and could be used for diagnostic assays detecting RSV.
PubMed: 38276631
DOI: 10.3390/tropicalmed9010001