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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 -
Pediatrics May 2019Palivizumab prophylaxis is used as passive immunization for respiratory syncytial virus (RSV). However, because of its high cost, the value of this intervention is...
CONTEXT
Palivizumab prophylaxis is used as passive immunization for respiratory syncytial virus (RSV). However, because of its high cost, the value of this intervention is unclear.
OBJECTIVE
To systematically review the cost-effectiveness of palivizumab prophylaxis compared with no prophylaxis in infants <24 months of age.
DATA SOURCES
Medline, Embase, and Cochrane Library up to August 2018.
STUDY SELECTION
Two reviewers independently screened results to include economic evaluations conducted between 2000 and 2018 from Organization for Economic Cooperation and Development countries.
DATA EXTRACTION
Two reviewers independently extracted outcomes. Quality appraisal was completed by using the Joanna Briggs Institute checklist. Costs were adjusted to 2017 US dollars.
RESULTS
We identified 28 economic evaluations (20 cost-utility analyses and 8 cost-effectiveness analyses); most were from the United States ( = 6) and Canada ( = 5). Study quality was high; 23 studies met >80% of the Joanna Briggs Institute criteria. Palivizumab prophylaxis ranged from a dominant strategy to having an incremental cost-effectiveness ratio of $2 526 203 per quality-adjusted life-year (QALY) depending on study perspective and targeted population. From the payer perspective, the incremental cost-effectiveness ratio for preterm infants (29-35 weeks' gestational age) was between $5188 and $791 265 per QALY, with 90% of estimates <$50 000 per QALY. Influential parameters were RSV hospitalization reduction rates, palivizumab cost, and discount rate.
LIMITATIONS
Model design heterogeneity, model parameters, and study settings were barriers to definitive conclusions on palivizumab's economic value.
CONCLUSIONS
Palivizumab as RSV prophylaxis was considered cost-effective in prematurely born infants, infants with lung complications, and infants from remote communities.
Topics: Antiviral Agents; Cost-Benefit Analysis; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 31040196
DOI: 10.1542/peds.2018-4064 -
World Journal of Pediatrics : WJP Nov 2010Palivizumab has proven efficacy for prophylaxis of respiratory syncytial virus (RSV) in infants with prematurity or congenital heart disease. Despite a paucity of data,... (Review)
Review
BACKGROUND
Palivizumab has proven efficacy for prophylaxis of respiratory syncytial virus (RSV) in infants with prematurity or congenital heart disease. Despite a paucity of data, palivizumab is sometimes used to prevent progression when high-risk patients present with upper respiratory tract infection (URTI) due to RSV, or as therapy when any patients present with severe lower respiratory tract infection (LRTI) caused by RSV.
METHODS
A systematic review of the literatures on the use of palivizumab as therapy for RSV was conducted. The primary outcomes were progression from URTI to LRTI and survival rates. Secondary outcomes were adverse events due to palivizumab, serum palivizumab level, and RSV concentration in respiratory secretions.
RESULTS
The search yielded 1 case report, 4 case series, and 2 randomized controlled trials (RCTs) with a total of 136 adults and children. The RCTs were not powered to look at clinical outcomes. By combining all reported clinical outcomes, 3 (12%) of 25 patients with URTI who were given palivizumab died of RSV and 5 of 88 patients with LRTI at the time of treatment died of RSV (6%). Palivizumab levels appeared to be adequate for at least 3 weeks of intravenous injection at 15 mg/kg. The therapy resulted in decreased RSV concentrations in tracheal secretions.
CONCLUSION
Larger RCTs will be required before palivizumab can be recommended as therapy for RSV in any clinical setting.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Humans; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 21080142
DOI: 10.1007/s12519-010-0230-z -
The Journal of Infectious Diseases Aug 2022Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of...
BACKGROUND
Since the widespread adoption of palivizumab prophylaxis in Europe, there have been a number of clinical practice guidelines (CPGs) published for the prevention of respiratory syncytial virus (RSV) infection in children. The aim of this systematic review was to identify CPGs for the prevention of RSV infection across Europe.
METHODS
We performed a systematic literature search and contacted European influenza and respiratory virus networks and public health institutions, to identify national CPGs for the prevention of RSV infection. The Reporting Items for practice Guidelines in Healthcare (RIGHT) Statement checklist was applied to extract data and review the quality of reporting.
RESULTS
A total of 20 national CPGs were identified, all published between 2000 and 2018. The greatest discrepancy between guidelines was the recommendations for palivizumab prophylaxis for premature infants, with recommendations varying by gestational age. All guidelines recommended or considered the use of palivizumab in infants with bronchopulmonary dysplasia, 85% (n = 17) in children with congenital heart disease (CHD), and 60% (n = 12) in children with severe combined immunodeficiency.
CONCLUSIONS
We recommend that agencies publishing RSV prevention guidelines adopt the RIGHT reporting requirements when updating these guidelines to improve the presentation of the evidence-base for decisions.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Hospitalization; Humans; Infant; Infant, Newborn; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 35333332
DOI: 10.1093/infdis/jiac059 -
Journal of Medical Economics 2010Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The... (Review)
Review
OBJECTIVE
Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The objective was to systematically examine the cost effectiveness of palivizumab in defined infant groups and identify important cost and outcome determinants.
METHODS
Literature searches of MedLine, the Cost-Effectiveness Analysis registry and the UK NHS Economic Evaluation Database (NHS EED) were conducted to identify economic evaluations of palivizumab compared to no prophylactic treatment for RSV prevention in any infant population. Study quality was evaluated using Quality of Health Economic Studies (QHES) criteria and results converted to 2009 CAN$ for comparison.
RESULTS
A total of 23 articles meeting inclusion criteria were identified, including 11 cost-utility analyses (CUAs) and 12 cost-effectiveness analyses (CEAs). Quality of individual analyses was fairly high (range 60-100, median 86). Results ranged from cost dominance for prophylaxis to $3,365,769/QALY depending on population, outcome measures, and input parameters. Base-case and sensitivity-analysis mortality rates varied between studies and influenced results.
CONCLUSIONS
RSV prophylaxis with palivizumab is cost effective in specific groups of high-risk infants, especially those with multiple environmental risk factors. Cost-effectiveness estimates vary between populations and settings and are more positive in those at highest risk for RSV hospitalization.
LIMITATIONS
Direct comparison of the published reports was limited by restriction to English language articles and the varied methodologies, input measures, and populations across the studies reviewed. Although reported currencies were converted to a common unit for comparison, this does not completely account for monetary and inflation differences.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Chemoprevention; Cost-Benefit Analysis; Humans; Infant; Palivizumab; Respiratory Syncytial Virus Infections
PubMed: 20653398
DOI: 10.3111/13696998.2010.499749 -
Pediatric Pulmonology Jan 2022The seasonality of respiratory syncytial virus (RSV) epidemics have been disrupted during the COVID-19 pandemic, possibly because of lockdowns and social restrictions...
BACKGROUND
The seasonality of respiratory syncytial virus (RSV) epidemics have been disrupted during the COVID-19 pandemic, possibly because of lockdowns and social restrictions reducing viral transmission. Given uncertainties around the severity of upcoming RSV bronchiolitis epidemics, debate exists whether palivizumab (RSV prophylaxis) should be administered to infants with Congenital Diaphragmatic Hernia (CDH), who may be vulnerable due to lung hypoplasia and pulmonary hypertension.
AIM
To evaluate (1) if CDH infants have higher risk of admission with RSV bronchiolitis than infants in the general population; (2) if palivizumab prophylaxis may reduce this risk.
METHODS
We included all eligible studies examining the risk(s) of RSV-positive bronchiolitis requiring hospital admission in (1) CDH infants without palivizumab prophylaxis versus infants in the general population and (2) CDH infants with prophylaxis versus CDH infants without prophylaxis. The primary outcome evaluated was the risk of admission with RSV bronchiolitis. Data are reported descriptively and meta-analysed when appropriate.
RESULTS
Three eligible retrospective cohort studies were identified: one study found CDH to be an independent risk factor for RSV hospitalisation (odds ratio, 3.30; 95% confidence interval [CI], 2.01-4.4); two studies compared RSV hospitalisation rates in CDH patients who had palivizumab versus those that did not. The pooled risk ratio was 1.11 (95% CI, 0.29-4.23; p = .88). Overall, the quality of evidence was considered poor and one study was industry funded.
CONCLUSION
Whether CDH infants are at particular risk of severe bronchiolitis remains unclear. There is no evidence from this current systematic review that CDH infants should routinely receive palivizumab vaccination prophylaxis.
Topics: Antiviral Agents; Bronchiolitis; COVID-19; Communicable Disease Control; Hernias, Diaphragmatic, Congenital; Hospitalization; Humans; Infant; Palivizumab; Pandemics; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies; SARS-CoV-2
PubMed: 34617409
DOI: 10.1002/ppul.25717 -
PharmacoEconomics 2010Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including... (Review)
Review
Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced-potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV-IGIV and palivizumab are associated with high acquisition costs. Cost-effectiveness analyses are therefore of great importance in helping to determine who should receive RSV prophylaxis. Six studies have analysed the cost effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab and five have analysed the cost effectiveness of both agents, two of which directly compared palivizumab with RSV-IGIV. The cost effectiveness of motavizumab has not been studied. Significant variation exists in the modelling used in these analyses. Many studies have examined short-term benefits such as reducing hospitalizations and associated costs, while fewer studies have examined long-term benefits such as QALYs or life-years gained. The payer and society have been the most common perspectives used. The endpoints examined varied and generally did not account for the potential impact of RSV prophylaxis on RSV-related complications such as asthma. While some studies have reported acceptable cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost savings or cost-effectiveness ratios below commonly accepted thresholds for either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to be more favourable in populations with specific risk factors, including premature infants < or =32 weeks' gestational age, and infants or children aged < 2 years with chronic lung disease or congenital heart disease. Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended. Over time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may decrease, and more acceptable outcomes of economic analyses may result. Albeit important, the results of economic analyses are not the only tool that decision makers rely on, as population-specific risk factors, and efficacy and safety data must be considered when developing treatment guidelines and making clinical decisions.
Topics: Antibodies; Cost-Benefit Analysis; Humans; Models, Economic; Respiratory Syncytial Virus Infections
PubMed: 20131925
DOI: 10.2165/11531860-000000000-00000 -
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 -
Respiratory Care Mar 2003Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and... (Review)
Review
Respiratory syncytial virus, the leading cause of serious upper and lower respiratory tract infection in infants and children, accounts for 125,000 hospitalizations and 450 deaths annually in the United States. It also may predispose to development of asthma later in life. Annual epidemics occur from November to April, and virtually all infants are infected by age 2. Immunity is not durable; hence, reinfection occurs throughout life, although subsequent infections are nearly always mild. Certain populations (eg, premature infants, infants with chronic lung disease, and immunocompromised individuals) are at risk for severe morbidity and have higher risk of mortality. Infection is spread to the nose and eyes by large droplets and direct contact with secretions, and fomites may remain infectious for up to 12 hours. Nosocomial infection is common. The virus infects airway ciliated epithelial cells, spreading by the formation of syncytia. Cellular debris and inflammation cause airway obstruction, hyperinflation, localized atelectasis, wheezing, and impaired gas exchange. Both humoral and cellular immune response are critical to ending the acute infection, but wheezing and reactive airways may persist for as long as 5-10 years after acute infection. No cure exists for respiratory syncytial virus infection, but commonly employed palliative treatments include oxygen, inhaled beta(2) agonists, racemic epinephrine, dornase alfa, systemic and inhaled corticosteroids, inhaled ribavirin, and nasopharyngeal suctioning. Infants suffering severe lower airways disease may require mechanical ventilation. Prophylactic measures include rigorous infection control and administration of polyclonal (RSV-IGIV [respiratory syncytial virus - immunoglobulin intravenous]) and monoclonal (palivizumab) antibodies. The cost of the prophylactic antibody treatment is high; it is cost-effective for only the highest risk patients. Development of a vaccine remains far in the future. Application of evidence-based clinical practice guidelines is making both out-patient and in-patient therapy as effective and economical as possible.
Topics: Disease Management; Humans; Infant; Infant, Newborn; Respiratory Syncytial Virus Infections; Respiratory Therapy; Risk Factors; United States
PubMed: 12667273
DOI: No ID Found -
Journal of the Pediatric Infectious... Feb 2024Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting...
BACKGROUND
Palivizumab is recommended for prevention of severe respiratory syncytial virus (RSV) disease in immunocompromised children, despite a lack of strong supporting evidence. The recent approval of substitute RSV-neutralizing monoclonal antibodies against RSV, offers an opportunity to synthesize the most current evidence supporting the palivizumab standard of care.
OBJECTIVE
To evaluate the efficacy of palivizumab in preventing acute respiratory tract infection- or RSV-related hospitalization, or mortality in immunocompromised children.
METHODS
We searched Ovid MEDLINE and EMBASE for published clinical studies that investigated outcomes of palivizumab use in children. We included clinical trials, cohort studies, and case-control studies. The primary outcomes were RSV-related or respiratory viral infection-related hospitalizations, or RSV-related mortality. This systematic review was registered in PROSPERO (ID CRD42021248619) and is reported in accordance with the PRISMA guidelines.
RESULTS
From the 1993 records, six studies were eligible and included, for a total of 625 immunocompromised children with an heterogeneous composition of primary and acquired immunodeficiencies enrolled from palivizumab programs. There were no intervention studies. None of the studies included a control group. RSV hospitalizations were infrequent (0%-3.1% of children). Most children included received palivizumab, although one study (n = 56) did not specify how many received palivizumab. RSV mortality was neither observed, in three studies, nor reported, in three other studies.
CONCLUSIONS
The evidence supporting the use of palivizumab for prevention of severe RSV disease in immunocompromised children remains extremely limited and appears insufficient to justify prioritizing this intervention as the current standard of care over alternative interventions.
Topics: Child; Humans; Antibodies, Monoclonal, Humanized; Antiviral Agents; Hospitalization; Immunologic Deficiency Syndromes; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 38279954
DOI: 10.1093/jpids/piae004