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JAMA Network Open Feb 2023Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.
OBJECTIVE
To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.
DATA SOURCES
In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.
STUDY SELECTION
Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.
MAIN OUTCOMES AND MEASURES
The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.
RESULTS
Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.
CONCLUSIONS AND RELEVANCE
In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.
Topics: Male; Infant; Child; Humans; Antibodies, Monoclonal; Palivizumab; Respiratory Syncytial Viruses; Network Meta-Analysis; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Oxygen; Randomized Controlled Trials as Topic
PubMed: 36800182
DOI: 10.1001/jamanetworkopen.2023.0023 -
The Cochrane Database of Systematic... Nov 2021Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus... (Review)
Review
BACKGROUND
Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population. Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children. Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children.
OBJECTIVES
To assess the effects of palivizumab for preventing severe RSV infection in children.
SEARCH METHODS
We searched CENTRAL, MEDLINE, three other databases and two trials registers to 14 October 2021, together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), including cluster-RCTs, comparing palivizumab given at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of age from both genders, regardless of RSV infection history. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results. Two review authors screened studies for selection, assessed risk of bias and extracted data. We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay, RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days.
MAIN RESULTS
We included five studies with a total of 3343 participants. All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumab every month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low. Palivizumab reduces hospitalisation due to RSV infection at two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64; 5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortality at two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15; 5 studies, 3343 participants; moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39; 3 studies, 2831 participants; moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reduction in hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97; 5 studies, 3343 participants; moderate certainty evidence). Palivizumab may result in a large reduction in RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55; 3 studies, 554 participants; low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces the number of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44; 1 study, 429 participants; high certainty evidence).
AUTHORS' CONCLUSIONS
The available evidence suggests that prophylaxis with palivizumab reduces hospitalisation due to RSV infection and results in little to no difference in mortality or adverse events. Moreover, palivizumab results in a slight reduction in hospitalisation due to respiratory-related illness and may result in a large reduction in RSV infections. Palivizumab also reduces the number of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumab on children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, children lacking breastfeeding, living in poverty, or members of families in overcrowded situations.
Topics: Child; Child, Preschool; Hospitalization; Humans; Infant; Infant, Newborn; Length of Stay; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 34783356
DOI: 10.1002/14651858.CD013757.pub2 -
BMJ Clinical Evidence Apr 2011Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate... (Review)
Review
INTRODUCTION
Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate climates and in the rainy season in warmer countries. Bronchiolitis is a common reason for attendance at and admission to hospital.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic interventions for bronchiolitis in high-risk children? What are the effects of measures to prevent transmission of bronchiolitis in hospital? What are the effects of treatments for children with bronchiolitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 59 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bronchodilators (oral, inhaled salbutamol, inhaled adrenaline [epinephrine], hypertonic saline), chest physiotherapy, continuous positive airway pressure, corticosteroids, fluid management, heliox, montelukast, nasal decongestants, nursing interventions (cohort segregation, hand washing, gowns, masks, gloves, and goggles), oxygen, respiratory syncytial virus immunoglobulins, pooled immunoglobulins, or palivizumab (monoclonal antibody), ribavirin, or surfactants.
Topics: Acute Disease; Administration, Inhalation; Albuterol; Bronchiolitis; Bronchodilator Agents; Double-Blind Method; Epinephrine; Humans; Infant
PubMed: 21486501
DOI: No ID Found -
BMJ Clinical Evidence Oct 2007Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate... (Review)
Review
INTRODUCTION
Bronchiolitis is the most common lower respiratory tract infection in infants, occurring in a seasonal pattern, with highest incidence in the winter in temperate climates, and in the rainy season in warmer countries. Bronchiolitis is a common reason for attendance at and admission to hospital.
METHODS AND OBJECTIVES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of prophylactic interventions for bronchiolitis in high-risk children? What are the effects of measures to prevent transmission of bronchiolitis in hospital? What are the effects of treatments for children with bronchiolitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: bronchodilators (oral, inhaled salbutamol, inhaled adrenaline [epinephrine]), chest physiotherapy, corticosteroids, montelukast, nursing interventions (cohort segregation, hand washing, gowns, masks, gloves, and goggles), respiratory syncytial virus immunoglobulins, pooled immunoglobulins, or palivizumab (monoclonal antibody), ribavirin, or surfactants.
Topics: Administration, Inhalation; Albuterol; Bronchiolitis; Bronchodilator Agents; Epinephrine; Hospitalization; Humans; Infant; Respiratory Syncytial Virus Infections
PubMed: 19450362
DOI: No ID Found -
Reviews in Medical Virology May 2022Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking... (Review)
Review
Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.
Topics: Antibodies, Monoclonal; Antiviral Agents; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34543489
DOI: 10.1002/rmv.2284 -
Infectious Diseases and Therapy Dec 2014Lower respiratory tract infection (LRTI) is the leading cause of infant mortality globally in post-neonatal infants (i.e., 28-364 days of age). Respiratory syncytial... (Review)
Review
INTRODUCTION
Lower respiratory tract infection (LRTI) is the leading cause of infant mortality globally in post-neonatal infants (i.e., 28-364 days of age). Respiratory syncytial virus (RSV) is the most commonly identified pathogen for infant LRTI and is the second most important cause of death in post-neonatal infants. Despite 50 years of RSV vaccine research, there is still no approved vaccine. Therefore, passive immunity with the monoclonal antibody palivizumab is the sole regulatory-approved option for the prevention of serious LRTI caused by RSV in pediatric patients at high risk of RSV disease.
METHODS
We conducted a comprehensive systematic literature review of randomized controlled trials (RCTs), open-label non-comparative clinical trials, and prospective observational studies/registries, and summarized the evidence related to the safety, efficacy, and effectiveness of palivizumab.
RESULTS
The efficacy of palivizumab, as measured by the relative reduction in RSV-related hospitalization rate compared with placebo ranged from 39% to 78% (P < 0.05) in the 2 pivotal RCTs. A meta-analysis of the RSV-related hospitalization rate from 5 randomized placebo-controlled trials yielded an overall odds ratio of 0.41 (95% CI, 0.31-0.55) in favor of palivizumab prophylaxis over placebo (P < 0.00001). Low rates of RSV-related hospitalizations were observed in palivizumab recipients consistently over time in more than 42,000 pediatric subjects across 7 RCTs, 4 open-label non-comparative trials, and 8 observational studies/registries conducted in 34 countries. In addition, among palivizumab-prophylaxed subjects with breakthrough RSV LRTI, rates of intensive care unit admission and mechanical ventilation from RSV hospitalization also were low and consistent across studies. With respect to safety, no differences were observed between palivizumab and placebo in the blinded RCTs.
CONCLUSION
Rates of RSV hospitalizations and RSV hospitalization-related endpoints in pediatric subjects who received prophylaxis with palivizumab were low and constant over time and across RCTs, open-label non-comparative trials, and observational studies/registries.
PubMed: 25297809
DOI: 10.1007/s40121-014-0046-6 -
Health Technology Assessment... Dec 2008To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine... (Review)
Review
OBJECTIVES
To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine prognostic factors to determine whether subgroups can be identified with important differences in cost-effectiveness.
DATA SOURCES
Bibliographic databases were searched from inception to March 2007 for literature on the effectiveness and cost-effectiveness of prophylaxis with palivizumab.
REVIEW METHODS
The literature was systematically reviewed and current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best estimates thought most applicable to the UK. We also constructed a new model, the Birmingham Economic Evaluation (BrumEE). Cost-effectiveness analyses were undertaken from both NHS and societal perspectives.
RESULTS
Two randomised controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission: 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group (p = 0.0004). Prophylaxis with palivizumab was associated with a 45% reduction in hospitalisation rate RSV among children with coronary heart disease (CHD). Hospitalisation rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group (p = 0.003). Of existing economic evaluations, 3 systematic reviews and 18 primary studies were identified. All the systematic reviews concluded that the potential costs of palivizumab were far in excess of any potential savings achieved by decreasing hospital admission rates, and that the use of palivizumab was unlikely to be cost-effective in all children for whom it is recommended, but that its continued use for particularly high-risk children may be justified. The incremental cost-effectiveness ratios (ICERs) of the primary studies varied 17-fold for life-years gained (LYG), from 25,800 pounds/LYG to 404,900 pounds/LYG, and several hundred-fold for quality-adjusted life-years (QALYs), from 3200 pounds/QALY to 1,489,700 pounds/QALY for preterm infants without CLD or children with CLD. For children with CHD, the ICER varied from 5300 pounds/LYG to 7900 pounds/LYG and from 7500 pounds/QALY to 68,700 pounds/QALY. An analysis of what led to the discrepant ICERs showed that the assumed mortality rate for RSV infection was the most important driver. The results of the BrumEE confirm that palivizumab does not reach conventional levels of cost-effectiveness in any of the licensed indications if used for all eligible children.
CONCLUSIONS
Prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population, the ICER is double that considered to represent good value for money in the UK. The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of 30,000 pounds/QALY) for children with CLD when the children have two or more additional risk factors. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD and then on primary research to address the important uncertainties that remain.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Palivizumab; Preventive Medicine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United Kingdom
PubMed: 19049692
DOI: 10.3310/hta12360 -
Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479 -
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 -
BMC Medicine Mar 2023Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a...
BACKGROUND
Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a shortacting monoclonal antibody (mAb), palivizumab (PVZ) that is expensive and intensive to administer, making it poorly suited for low-resource settings. Currently, new longer acting RSV mAbs and maternal vaccines are emerging from late-stage clinical development with promising clinical effectiveness. However, evidence of economic value and affordability must also be considered if these interventions are to be globally accessible. This systematic review's objective was to summarise existing evidence on the cost-of-illness (COI) and cost-effectiveness of RSV prevention interventions in LMICs.
METHODS
We conducted a systematic literature review using the Embase, MEDLINE, and Global Index Medicus databases for publications between Jan 2000 and Jan 2022. Two categories of studies in LMICs were targeted: cost-of-illness (COI) of RSV episodes and cost-effectiveness analyses (CEA) of RSV preventive interventions including maternal vaccines and long-acting mAbs. Of the 491 articles reviewed, 19 met the inclusion criteria.
RESULTS
COI estimates varied widely: for severe RSV, the cost per episode ranged from $92 to $4114. CEA results also varied-e.g. evaluations of long-acting mAbs found ICERs from $462/DALY averted to $2971/DALY averted. Study assumptions of input parameters varied substantially and their results often had wide confidence intervals.
CONCLUSIONS
RSV represents a substantial disease burden; however, evidence of economic burden is limited. Knowledge gaps remain regarding the economic value of new technologies specifically in LMICs. Further research is needed to understand the economic burden of childhood RSV in LMICs and reduce uncertainty about the relative value of anticipated RSV prevention interventions. Most CEA studies evaluated palivizumab with fewer analyses of interventions in development that may be more accessible for LMICs.
Topics: Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Antibodies, Monoclonal; Cost-Effectiveness Analysis
PubMed: 37004038
DOI: 10.1186/s12916-023-02792-z