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The Cochrane Database of Systematic... Oct 2023Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled... (Review)
Review
BACKGROUND
Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled bronchodilators, epinephrine, nebulised hypertonic saline, and corticosteroids) are ineffective or have limited effect. Respiratory syncytial virus immunoglobulin may be used prophylactically to prevent hospital admission from RSV-related illness. It may be considered for the treatment of established severe RSV infection or for treatment in an immunocompromised host, although it is not licensed for this purpose. It is unclear whether immunoglobulins improve outcomes when used as a treatment for established RSV infection in infants and young children admitted to hospital. This is an update of a review first published in 2019.
OBJECTIVES
To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections (LRTIs) in children aged up to three years, admitted to hospital.
SEARCH METHODS
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 2 December 2022) with no restrictions. We searched two trial registries for ongoing trials (to 2 December 2022) and checked the reference lists of reviews and included articles for additional studies.
SELECTION CRITERIA
Randomised controlled trials comparing immunoglobulins with placebo in hospitalised infants and children aged up to three years with laboratory-diagnosed RSV lower respiratory tract infection.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed risk of bias, and extracted data. We assessed evidence certainty using GRADE.
MAIN RESULTS
In total, we included eight trials involving 906 infants and children aged up to three years. We included one new trial in this update. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. Five trials were conducted at single or multiple sites within a single high-income country (four in the USA, one in Qatar). Three trials included study sites in different countries. All three of these trials included study sites in one or more high-income countries (USA, Chile, New Zealand, Australia, Qatar), with two trials also including a study site in a middle-income country (Panama). Five of the eight trials were "supported" or "sponsored" by the trial drug manufacturers. The evidence is very uncertain about the effect of immunoglobulins on mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 4 studies, 309 participants). There were four deaths - two amongst 98 children receiving immunoglobulins, and two amongst 98 children receiving placebo. One additional death occurred in a fourth trial, however the study group of the child was not known and the data were not included in the analysis (very low-certainty evidence). The use of immunoglobulins in infants and children admitted to hospital with RSV proven LRTI probably results in little to no difference in the length of hospitalisation (mean difference (MD) -0.13 days, 95% CI -0.37 to 0.12; 6 studies, 737 participants; moderate-certainty evidence). Immunoglobulins may result in little to no difference in the number of children who experience one or more adverse events of any severity or seriousness compared to placebo (RR 1.18, 95% CI 0.78 to 1.78; 5 studies, 340 participants; low-certainty evidence) or the number of children who experience one or more adverse events judged by study investigators to be serious in nature, compared to placebo (RR 1.08, 95% CI 0.65 to 1.79; 4 studies, 238 participants; low-certainty evidence). Certainty of evidence for secondary outcomes was low. This evidence suggests that use of immunoglobulins results in little to no difference in the need for, or duration of, mechanical ventilation and the need for, or duration of, supplemental oxygen. The use of immunoglobulins does not reduce the need for admission to the intensive care unit (ICU) and when children are admitted to the ICU results in little to no difference in the duration of ICU stay.
AUTHORS' CONCLUSIONS
We are very uncertain about the effect of immunoglobulins on mortality. We are moderately certain that use of immunoglobulins in hospitalised infants and children may result in little to no difference in the length of hospitalisation. Immunoglobulins may result in little to no difference in adverse events, the need for or duration of mechanical ventilation, supplemental oxygen, or admission to the intensive care unit, though we are less certain about this evidence and the true effect of immunoglobulins on these outcomes may differ markedly from the estimated effect observed in this review. All trials were conducted in high-income countries, and data from populations in which the rate of death from RSV infection is higher are lacking.
Topics: Infant; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Hospitalization; Adrenal Cortex Hormones; Respiratory Tract Infections; Oxygen
PubMed: 37870128
DOI: 10.1002/14651858.CD009417.pub3 -
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 -
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 -
Italian Journal of Pediatrics Nov 2019The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the...
Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016-2017 epidemic season: a systematic review of seven...
BACKGROUND
The only pharmacologic prophylaxis against respiratory syncytial virus (RSV) infection in preterm infants is the humanized monoclonal antibody palivizumab. After the 2014 modification of the American Academy of Pediatrics (AAP) recommendations, the Italian Medicines Agency (AIFA) limited the financial coverage for palivizumab prescriptions to otherwise healthy preterm infants with < 29 weeks of gestational age (wGA) aged < 12 months at the beginning of the 2016-2017 RSV season. However, due to the effect on disease severity and hospitalizations following this limitation, shown by several Italian clinical studies, in November 2017 AIFA reinstated the financial coverage for these infants. In this systematic review, we critically summarize the data that show the importance of palivizumab prophylaxis.
METHODS
Data from six Italian pediatric institutes and the Italian Network of Pediatric Intensive Care Units (TIPNet) were retrieved from the literature and considered. The epidemiologic information for infants 29-36 wGA, aged < 12 months and admitted for viral-induced acute lower respiratory tract infection were retrospectively reviewed. RSV-associated hospitalizations were compared between the season with running limitation, i.e. 2016-2017, versus 2 seasons before (2014-2015 and 2015-2016) and one season after (2017-2018) the AIFA limitation.
RESULTS
During the 2016-2017 RSV epidemic season, when the AIFA limited the financial coverage of palivizumab prophylaxis based on the 2014 AAP recommendation, the study reports on a higher incidences of RSV bronchiolitis and greater respiratory function impairment. During this season, we also found an increase in hospitalizations and admissions to the Pediatric Intensive Care Units and longer hospital stays, incurring higher healthcare costs. During the 2016-2017 epidemic season, an overall increase in the number of RSV bronchiolitis cases was also observed in infants born full term, suggesting that the decreased prophylaxis in preterm infants may have caused a wider infection diffusion in groups of infants not considered to be at risk.
CONCLUSIONS
The Italian results support the use of palivizumab prophylaxis for otherwise healthy preterm (29-36 wGA) infants aged < 6 months at the beginning of the RSV season.
Topics: Antiviral Agents; Epidemics; Health Care Costs; Hospitalization; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Italy; Palivizumab; Respiratory Syncytial Virus Infections; United States
PubMed: 31706338
DOI: 10.1186/s13052-019-0736-5 -
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 -
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 -
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 -
The Pediatric Infectious Disease Journal Oct 2016To systematically review the effectiveness of preventative and therapeutic interventions for respiratory tract infections (RTIs) in people with Down's syndrome. (Review)
Review
AIMS
To systematically review the effectiveness of preventative and therapeutic interventions for respiratory tract infections (RTIs) in people with Down's syndrome.
METHODS
Databases were searched for any published and ongoing studies of respiratory tract diseases in children and adults with Down's syndrome. These databases were searched for controlled trials, cohort studies and controlled before-after studies. Trial registries were searched for ongoing studies. Initially, all study types were included to provide a broad overview of the existing evidence base. However, those with a critical risk of bias were excluded using the Cochrane Risk of Bias tool.
RESULTS
A total of 13,575 records were identified from which 5 studies fulfilled the eligibility criteria and 3 fulfilled our criteria for data extraction. One randomized controlled trial of moderate risk of bias compared zinc therapy with placebo. Outcome data were only reported for 50 (78%) children who presented with extreme symptoms; no benefit of zinc therapy was found. One non-randomized controlled trial with serious risk of bias included 26 children and compared pidotimod (an immunostimulant) with no treatment; pidotimod was associated with fewer upper RTI recurrences compared with no treatment (1.43 vs. 3.82). A prospective cohort study with moderate risk of bias compared 532 palivizumab treated children with 233 untreated children and found that children treated with palivizumab had fewer respiratory syncytial virus-related hospitalization (23 untreated and 8 treated), but the same number of overall RTI-related hospitalizations (73 untreated and 74 treated) in the first 2 years of life.
CONCLUSIONS
The evidence base for the management of RTIs in people with Down's syndrome is incomplete; current studies included children only and carry a moderate to serious risk of bias. Methodologic rigorous studies are warranted to guide clinicians in how best to prevent and treat RTIs in children with Down's syndrome.
Topics: Anti-Infective Agents; Bias; Clinical Trials as Topic; Down Syndrome; Humans; Palivizumab; Pyrrolidonecarboxylic Acid; Respiratory Tract Infections; Thiazolidines; Zinc
PubMed: 27273687
DOI: 10.1097/INF.0000000000001243 -
Influenza and Other Respiratory Viruses Jul 2016Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We... (Review)
Review
Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We reviewed published and unpublished literature from hospital settings to assess: (i) nosocomial RSV transmission risk (attack rate) during outbreaks, (ii) effectiveness of infection control measures. We searched the following databases: MEDLINE, EMBASE, CINAHL, Cochrane Library, together with key websites, journals and grey literature, to end of 2012. Risk of bias was assessed using the Cochrane risk of bias tool or Newcastle-Ottawa scale. A narrative synthesis was conducted. Forty studies were included (19 addressing research question one, 21 addressing question two). RSV transmission risk varied by hospital setting; 6-56% (median: 28·5%) in neonatal/paediatric settings (n = 14), 6-12% (median: 7%) in adult haematology and transplant units (n = 3), and 30-32% in other adult settings (n = 2). For question two, most studies (n = 13) employed multi-component interventions (e.g. cohort nursing, personal protective equipment (PPE), isolation), and these were largely reported to be effective in reducing nosocomial transmission. Four studies examined staff PPE; eye protection appeared more effective than gowns and masks. One study reported on RSV prophylaxis for patients (RSV-Ig/palivizumab); there was no statistical evidence of effectiveness although the sample size was small. Overall, risk of bias for included studies tended to be high. We conclude that RSV transmission risk varies widely during hospital outbreaks. Although multi-component control strategies appear broadly successful, further research is required to disaggregate the effectiveness of individual components including the potential role of palivizumab prophylaxis.
Topics: Animals; Cross Infection; Humans; Infection Control; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 26901358
DOI: 10.1111/irv.12379 -
The Journal of Infectious Diseases Aug 2022The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
BACKGROUND
The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
METHODS
We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools.
RESULTS
We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012.
CONCLUSIONS
Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.
Topics: Bronchiolitis; Humans; Infant; Infant, Newborn; Infant, Premature; Palivizumab; Patient Acceptance of Health Care; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United States
PubMed: 35968876
DOI: 10.1093/infdis/jiac201