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Acta Medica Academica Aug 2020This review addresses differences in respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) between industrialized and developing countries and... (Review)
Review
This review addresses differences in respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) between industrialized and developing countries and provides observations associated with the dissimilar consequences of viral infection in both environments. RSV LRTI is an important cause of morbidity and mortality in infants worldwide. Its burden is highest in developing countries, where most hospitalizations and mortality occur. Palivizumab has been approved for disease prevention in premature infants in numerous countries but its cost and requirement for several doses hampers its routine use. The significant gap between low- and high-income countries in mortality rates stresses the need to identify specific risk factors for RSV LRTI prevention in different populations. CONCLUSION: RSV LTRI continues to be a serious problem for industrialised and developing countries, although mortality occurs preferentially in the latter. Several vaccines and monoclonal antibodies to prevent severe disease are advancing steadily in late phase trials. The next decade may witness a change in the landscape of RSV infections in young infants.
Topics: Antiviral Agents; Asthma; Bronchiolitis, Viral; Coinfection; Developing Countries; Drug Costs; Global Burden of Disease; Hospitalization; Humans; Infant, Premature; Palivizumab; Pneumonia; Respiratory Syncytial Virus Infections
PubMed: 33189124
DOI: 10.5644/ama2006-124.297 -
Frontiers in Immunology 2023Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion...
INTRODUCTION
Nirsevimab is an extended half-life (M252Y/S254T/T256E [YTE]-modified) monoclonal antibody to the pre-fusion conformation of the respiratory syncytial virus (RSV) Fusion protein, with established efficacy in preventing RSV-associated lower respiratory tract infection in infants for the duration of a typical RSV season. Previous studies suggest that nirsevimab confers protection via direct virus neutralization. Here we use preclinical models to explore whether fragment crystallizable (Fc)-mediated effector functions contribute to nirsevimab-mediated protection.
METHODS
Nirsevimab, MEDI8897* (i.e., nirsevimab without the YTE modification), and MEDI8897*-TM (i.e., MEDI8897* without Fc effector functions) binding to Fc γ receptors (FcγRs) was evaluated using surface plasmon resonance. Antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular cytotoxicity (ADCC) were assessed through and serological analyses. A cotton rat challenge study was performed with MEDI8897* and MEDI8897*-TM to explore whether Fc effector functions contribute to protection from RSV.
RESULTS
Nirsevimab and MEDI8897* exhibited binding to a range of FcγRs, with expected reductions in FcγR binding affinities observed for MEDI8897*-TM. Nirsevimab exhibited ADNP, ADCP, ADCD, and ADCC activity above background levels, and similar ADNP, ADCP, and ADCD activity to palivizumab. Nirsevimab administration increased ADNP, ADCP, and ADCD activity in participant serum from the MELODY study (NCT03979313). However, ADCC levels remained similar between nirsevimab and placebo. MEDI8897* and MEDI8897*-TM exhibited similar dose-dependent reduction in lung and nasal turbinate RSV titers in the cotton rat model.
CONCLUSION
Nirsevimab possesses Fc effector activity comparable with the current standard of care, palivizumab. However, despite possessing the capacity for Fc effector activity, data from RSV challenge experiments illustrate that nirsevimab-mediated protection is primarily dependent on direct virus neutralization.
Topics: Infant; Humans; Animals; Palivizumab; Antibodies, Viral; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Complement System Proteins; Sigmodontinae
PubMed: 37901217
DOI: 10.3389/fimmu.2023.1283120 -
Health Technology Assessment... Jan 2011Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in... (Review)
Review
Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.
BACKGROUND
Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children.
OBJECTIVES
To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection.
DATA SOURCES
A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched.
REVIEW METHODS
Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to find any relevant studies that may have been missed. The risk factors identified from the systematic review of included studies were analysed and synthesised using stata. The base-case decision tree model developed in the original HTA journal publication [Health Technol Assess 2008;12(36)] was used to derive the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of pre-term infants and young children who are at high risk of serious morbidity from RSV infection. Cost-effective spectra of prophylaxis with palivizumab compared with no prophylaxis for children without CLD/CHD, children with CLD, children with acyanotic CHD and children with cyanotic CHD were derived.
RESULTS
Thirteen studies were included in this analysis. Analysis of 16,128 subgroups showed that prophylaxis with palivizumab may be cost-effective [at a willingness-to-pay threshold of £30,000/quality-adjusted life-year (QALY)] for some subgroups. For example, for children without CLD or CHD, the cost-effective subgroups included children under 6 weeks old at the start of the RSV season who had at least two other risk factors that were considered in this report and were born at 24 weeks gestational age (GA) or less, but did not include children who were > 9 months old at the start of the RSV season or had a GA of > 32 weeks. For children with CLD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 28 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with acyanotic CHD, the cost-effective subgroups included children < 6 months old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 21 months old at the start of the RSV season. For children with cyanotic CHD, the cost-effective subgroups included children < 6 weeks old at the start of the RSV season who were born at 24 weeks GA or less, but did not include children who were > 12 months old at the start of the RSV season.
LIMITATIONS
The poor quality of the studies feeding numerical results into this analysis means that the true cost-effectiveness may vary considerably from that estimated here. There is a risk that the relatively high mathematical precision of the point estimates of cost-effectiveness may be quite inaccurate because of poor-quality inputs.
CONCLUSIONS
Prophylaxis with palivizumab does not represent good value for money based on the current UK incremental cost-effectiveness ratio threshold of £30,000/QALY when used unselectively in children without CLD/CHD or children with CLD or CHD. This subgroup analysis showed that prophylaxis with palivizumab may be cost-effective (at a willingness-to-pay threshold of £30,000/QALY) for some subgroups. In summary, the cost-effective subgroups for children who had no CLD or CHD must contain at least two other risk factors apart from GA and birth age. The cost-effective subgroups for children who had CLD or CHD do not necessarily need to have any other risk factors. Future research should be directed towards conducting much larger, better powered and better reported studies to derive better estimates of the risk factor effect sizes.
FUNDING
This report was funded by the HTA programme of the National Institute for Health Research.
Topics: Age Factors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis, Viral; Child, Preschool; Cost-Benefit Analysis; Female; Humans; Infant; Infant, Newborn; Male; Models, Economic; Palivizumab; Respiratory Syncytial Virus Infections; Risk Assessment
PubMed: 21281564
DOI: 10.3310/hta15050 -
Respiratory Medicine Apr 2002Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant... (Review)
Review
Respiratory syncytial virus (RSV) is a common and highly contagious pathogen that infects nearly all children by the age of 2 years. It is responsible for significant morbidity and mortality worldwide among certain high-risk paediatric populations. Therapy is sub-optimal for RSV, thus treatment focuses on ameliorating symptoms. Since discovery of the virus in the 1950s, efforts have been ongoing to develop a safe and effective vaccine. These efforts have met with serious obstacles. Passive immunoprophylaxis presents a viable alternative to active immunization. In 1998, the genetically engineered humanized monoclonal antibody (palivizumab) was granted FDA (Food and Drug Administration) approval for prophylaxis of high-risk children in the United States; EMEA (European Agency for the Evaluation of Medicinal Products) approval followed in 1999 for Europe. It is now approved in over 45 countries worldwide. Palivizumab was shown to significantly reduce RSV-related hospitalizations in North America and Europe with few adverse effects. Clinical trial and outcomes data documenting experience with palivizumab to date continue to extend the initial safety and efficacy observations.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cross Infection; Humans; Immunization, Passive; Infant; Infant, Newborn; Infant, Premature, Diseases; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Vaccines, Synthetic; Viral Vaccines
PubMed: 11996400
DOI: 10.1016/s0954-6111(02)90066-1 -
Infectious Diseases and Therapy Mar 2018The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory... (Review)
Review
INTRODUCTION
The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children.
METHODS
A systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library. Studies reporting data on the effectiveness and tolerability of prophylactic and therapeutic agents for RSV infection were included. Study quality and strength of evidence (SOE) were graded using recognized criteria. A further nonsystematic search of the published literature and Clinicaltrials.gov on antiviral therapies and RSV vaccines currently in development was also undertaken.
RESULTS
The systematic review identified 1441 studies of which 161 were included. Management of RSV remains centered around prophylaxis with the monoclonal antibody palivizumab, which has proven effective in reducing RSV hospitalization (RSVH) in preterm infants < 36 weeks' gestational age (72% reduction), children with bronchopulmonary dysplasia (65% reduction), and infants with hemodynamically significant congenital heart disease (53% reduction) (high SOE). Palivizumab has also shown to be effective in reducing recurrent wheezing following RSVH (high SOE). Treatment of RSV with ribavirin has conflicting success (moderate SOE). Antibodies with increased potency and extended half-life are currently entering phase 3 trials. There are approximately 15 RSV vaccines in clinical development targeting the infant directly or indirectly via the mother.
CONCLUSION
Palivizumab remains the only product licensed for RSV prophylaxis, and only available for high-risk infants. For the general population, there are several promising vaccines and monoclonal antibodies in various stages of clinical development, with the aim to significantly reduce the global healthcare impact of this common viral infection.
FUNDING
AbbVie.
PubMed: 29470837
DOI: 10.1007/s40121-018-0188-z -
The Journal of Pediatric Pharmacology... 2020Guidelines by the AAP for the use of palivizumab prophylaxis for respiratory syncytial virus (RSV) recommend administration within 72 hours prior to discharge for...
OBJECTIVES
Guidelines by the AAP for the use of palivizumab prophylaxis for respiratory syncytial virus (RSV) recommend administration within 72 hours prior to discharge for selected high-risk patient populations. Our institution historically administered palivizumab on a fixed-day schedule of Mondays and Thursdays, but adjusted the practice in fall 2017 to a pharmacist-driven flex-schedule based on anticipated discharge date. This review evaluated the effect of pharmacist-driven palivizumab ordering on the appropriateness of palivizumab administrations, based on AAP and institutional recommendations. Additionally, this review evaluated for effects on institutional cost.
METHODS
This was a retrospective single-center evaluation including patients for whom palivizumab was ordered between July 1, 2016, and June 30, 2018. Patients in the 2016-2017 RSV season were in the fixed-day group, while patients in the 2017-2018 RSV season were in the flex-schedule group.
RESULTS
A total of 142 palivizumab doses were evaluated. Overall, 97% of administrations were for an appropriate indication. All doses administered inappropriately (n = 4) occurred in the fixed-day group. In the fixed-day group, 48.6% of doses were given within 72 hours prior to discharge, which increased to 70.1% in the flex-schedule group (p = 0.01). The amount of drug saved by batching was 1 vial for every 4.9 patients in the fixed-day group, and 1 vial for every 4.8 patients in the flex-schedule group.
CONCLUSIONS
There was a statistically significant improvement in compliance with AAP recommendations following the implementation of pharmacist-driven flex-schedule for palivizumab, compared to a fixed-day batching schedule. There was no significant difference in cost.
PubMed: 33041719
DOI: 10.5863/1551-6776-25.7.636 -
Applied Clinical Informatics 2015Palivizumab can reduce hospitalizations due to respiratory syncytial virus (RSV), but many eligible infants fail to receive the full 5-dose series. The efficacy of...
BACKGROUND AND OBJECTIVES
Palivizumab can reduce hospitalizations due to respiratory syncytial virus (RSV), but many eligible infants fail to receive the full 5-dose series. The efficacy of clinical decision support (CDS) in fostering palivizumab receipt has not been studied. We sought a comprehensive solution for identifying eligible patients and addressing barriers to palivizumab administration.
METHODS
We developed workflow and CDS tools targeting patient identification and palivizumab administration. We randomized 10 practices to receive palivizumab-focused CDS and 10 to receive comprehensive CDS for premature infants in a 3-year longitudinal cluster-randomized trial with 2 baseline and 1 intervention RSV seasons.
RESULTS
There were 356 children eligible to receive palivizumab, with 194 in the palivizumab-focused group and 162 in the comprehensive CDS group. The proportion of doses administered to children in the palivizumab-focused intervention group increased from 68.4% and 65.5% in the two baseline seasons to 84.7% in the intervention season. In the comprehensive intervention group, proportions of doses administered declined during the baseline seasons (from 71.9% to 62.4%) with partial recovery to 67.9% during the intervention season. The palivizumab-focused group improved by 19.2 percentage points in the intervention season compared to the prior baseline season (p < 0.001), while the comprehensive intervention group only improved 5.5 percentage points (p = 0.288). The difference in change between study groups was significant (p = 0.05).
CONCLUSIONS
Workflow and CDS tools integrated in an EHR may increase the administration of palivizumab. The support focused on palivizumab, rather than comprehensive intervention, was more effective at improving palivizumab administration.
Topics: Decision Support Systems, Clinical; Female; Humans; Infant; Infant, Newborn; Male; Palivizumab; Patient Selection; Pregnancy; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Seasons; Workflow
PubMed: 26767069
DOI: 10.4338/ACI-2015-08-RA-0096 -
Frontiers in Medicine 2021Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this... (Review)
Review
Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.
PubMed: 34712683
DOI: 10.3389/fmed.2021.745665 -
Canadian Family Physician Medecin de... May 2008
Review
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis; Canada; Hospitalization; Humans; Infant; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 18474710
DOI: No ID Found -
Vaccines Dec 2023Respiratory Syncytial Virus (RSV) poses a severe threat to infants, particularly preterm infants. Palivizumab, the standard preventive prophylaxis, is primarily utilized...
Respiratory Syncytial Virus (RSV) poses a severe threat to infants, particularly preterm infants. Palivizumab, the standard preventive prophylaxis, is primarily utilized in high-risk newborns due to its cost. This study assessed palivizumab's effectiveness in preventing RSV infections in predominantly very preterm infants during their first year of life. Serum samples from a prospective multicentre cohort study in the Netherlands were analyzed to assess RSV infection rates by measuring IgG levels against three RSV proteins: nucleoprotein, pre-fusion, and post-fusion protein. Infants were stratified based on gestational age (GA), distinguishing very preterm (≤32 weeks GA) from moderate/late preterm (>32 to ≤36 weeks GA). In very preterm infants, palivizumab prophylaxis significantly reduced infection rates (18.9% vs. 48.3% in the prophylaxis vs. non-prophylaxis group. Accounting for GA, sex, birth season, and birth weight, the prophylaxis group showed significantly lower infection odds. In infants with >32 to ≤36 weeks GA, the non-prophylaxis group (55.4%) showed infection rates similar to the non-prophylaxis ≤32-week GA group, despite higher maternal antibody levels in the moderate/late preterm infants. In conclusion, palivizumab prophylaxis significantly reduces RSV infection rates in very premature infants. Future research should explore clinical implications and reasons for non-compliance, and compare palivizumab with emerging prophylactics like nirsevimab aiming to optimize RSV prophylaxis and improve preterm infant outcomes.
PubMed: 38140212
DOI: 10.3390/vaccines11121807