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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 -
The Cochrane Database of Systematic... May 2014Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 17 March 2014.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Cystic Fibrosis; Drug Administration Schedule; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 24851825
DOI: 10.1002/14651858.CD007743.pub5 -
The Cochrane Database of Systematic... Jun 2013Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 11 October 2012.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Cystic Fibrosis; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 23737087
DOI: 10.1002/14651858.CD007743.pub4 -
The Cochrane Database of Systematic... Apr 2013Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections in children. It results in about 3.4 million... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing acute respiratory infections in children. It results in about 3.4 million hospitalisations annually in children under five. Palivizumab is an anti-RSV monoclonal antibody, administered intramuscularly at a dose of 15 mg/kg once every 30 days. The efficacy and safety of palivizumab has been evaluated in multicentre, randomised controlled trials (RCTs) and a large number of economic evaluations (EEs) have tested its cost-effectiveness.
OBJECTIVES
To assess the effectiveness and safety of palivizumab prophylaxis compared with placebo, or another type of prophylaxis, in reducing the risk of complications (hospitalisation due to RSV infection) in high-risk infants and children. To assess the cost-effectiveness (or cost-utility) of palivizumab prophylaxis compared with no prophylaxis in infants and children in different risk groups.
SEARCH METHODS
We searched CENTRAL 2012, Issue 7, MEDLINE (1996 to July week 4, 2012), EMBASE (1996 to August 2012), CINAHL (1996 to August 2012) and LILACS (1996 to August 2012) for studies of effectiveness and safety. We searched the NHS Economic Evaluations Database (NHS EED 2012, Issue 4), Health Economics Evaluations Database (HEED, 9 August 2012) and Paediatric Economic Database Evaluations (PEDE, 1980 to 2009), MEDLINE (1996 to July week 4, 2012) and EMBASE (1996 to August 2012) for economic evaluations.
SELECTION CRITERIA
We included RCTs comparing palivizumab prophylaxis with a placebo, no prophylaxis or another type of prophylaxis in preventing serious lower respiratory tract disease caused by RSV in paediatric patients at high risk. We included cost-effectiveness analyses and cost-utility analyses comparing palivizumab prophylaxis with no prophylaxis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias for the included studies and extracted data for both the RCTs and EEs. We calculated risk ratios (RRs) and their associated 95% confidence intervals (CIs) for dichotomous outcomes and for adverse events (AEs). We provided a narrative summary of results for continuous outcomes, due to missing data on standard deviations. We performed fixed-effect meta-analyses for the estimation of pooled effects whenever there was no indication of heterogeneity between included RCTs. We summarised the results reported in included EEs, such as incremental costs, incremental effectiveness, and incremental cost-effectiveness and/or cost-utility ratios (ICERs), and we calculated ICER present values in 2011 Euros for all studies.
MAIN RESULTS
Of the seven available RCTs, three compared palivizumab with a placebo in a total of 2831 patients, and four compared palivizumab with motavizumab in a total of 8265 patients. All RCTs were sponsored by the drug manufacturing company. The overall quality of RCTs was good, but for most of the outcomes assessed only data from two studies contributed to the analysis. Palivizumab prophylaxis was associated with a statistically significant reduction in RSV hospitalisations (RR 0.49, 95% CI 0.37 to 0.64) when compared to placebo. When compared to motavizumab, palivizumab recipients showed a non-significant increase in the risk of RSV hospitalisations (RR 1.36, 95% CI 0.97 to 1.90). In both cases, the proportion of children with any AE or any AE related to the study drug was similar between the two groups.In terms of economic evidence, we included 34 studies that reported cost-effectiveness and/or cost-utility data for palivizumab prophylaxis compared with no prophylaxis, in high-risk children with different underlying medical conditions. The overall quality of EEs was good, but the variations in modelling approaches were considerable across the studies, leading to big differences in cost-effectiveness results. The cost-effectiveness of palivizumab prophylaxis depends on the consumption of resources taken into account by the study authors; and on the cost-effectiveness threshold set by the healthcare sector in each country.
AUTHORS' CONCLUSIONS
There is evidence that palivizumab prophylaxis is effective in reducing the frequency of hospitalisations due to RSV infection, i.e. in reducing the incidence of serious lower respiratory tract RSV disease in children with chronic lung disease, congenital heart disease or those born preterm.Results from economic evaluations of palivizumab prophylaxis are inconsistent, implying that economic findings must be interpreted with caution. ICER values varied considerably across studies, from highly cost-effective to not cost-effective. The availability of low-cost palivizumab would reduce its inequitable distribution, so that RSV prophylaxis would be available to the poorest countries where children are at greatest risk.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child, Preschool; Hospitalization; Humans; Infant; Infant, Newborn; Palivizumab; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 23633336
DOI: 10.1002/14651858.CD006602.pub4 -
The Cochrane Database of Systematic... Feb 2012Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children... (Review)
Review
BACKGROUND
Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis.
OBJECTIVES
To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 25 October 2011.
SELECTION CRITERIA
Randomised and quasi-randomised studies.
DATA COLLECTION AND ANALYSIS
The authors independently extracted data and assessed risk of bias.
MAIN RESULTS
One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.
AUTHORS' CONCLUSIONS
We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis because the trial did not specify how adverse events were classified. Six months after treatment, the authors reported no clinically meaningful differences in outcomes; however no data were provided. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Cystic Fibrosis; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 22336832
DOI: 10.1002/14651858.CD007743.pub3 -
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 -
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 -
Pediatric Critical Care Medicine : a... Sep 2011A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with... (Meta-Analysis)
Meta-Analysis Review
Mortality and morbidity among infants at high risk for severe respiratory syncytial virus infection receiving prophylaxis with palivizumab: a systematic literature review and meta-analysis.
OBJECTIVES
A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease).
DATA SOURCES
MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies.
STUDY SELECTION
Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab.
DATA EXTRACTION
Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis.
DATA SYNTHESIS
A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses.
CONCLUSIONS
Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.
Topics: Antibodies, Monoclonal, Humanized; Antiviral Agents; Humans; Infant; Morbidity; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Severity of Illness Index
PubMed: 21200358
DOI: 10.1097/PCC.0b013e3182070990 -
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 Cochrane Database of Systematic... Sep 2010Respiratory syncytial virus (RSV) bronchiolitis and pneumonia hospitalise hundreds of thousands of infants every year. Treatment is largely supportive therapy, (for... (Review)
Review
BACKGROUND
Respiratory syncytial virus (RSV) bronchiolitis and pneumonia hospitalise hundreds of thousands of infants every year. Treatment is largely supportive therapy, (for example, oxygen, fluids and occasionally mechanical ventilation). Ribavirin, an antiviral agent, is licensed for severe RSV infection, although systematic reviews find it of no benefit. Passive protection against RSV can be achieved through monthly intramuscular injections of the humanised monoclonal anti-RSV antibody palivizumab (Synagis), and yields a 55% reduction in RSV hospitalisation in susceptible infants. This review assesses immunoglobulin treatment of RSV infection rather than its role as a prophylactic measure.
OBJECTIVES
To assess the efficacy of adding human or humanised immunoglobulin therapy to supportive therapy in infants hospitalised with laboratory-determined RSV infection.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 1) which contains the Acute Respiratory Infections Group's specialized regsiter, MEDLINE (1966 to Week 4, January 2006) and EMBASE (1980 to September 2005). We also ran searches of reference lists of relevant trials and review articles and searches of personal files. We did not impose any language restrictions.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared immunoglobulin treatment with a placebo control in children hospitalised for RSV infection with bronchiolitis or pneumonia or other lower respiratory tract infection (LRTI) with laboratory-documented RSV infection. The primary outcomes of interest were mortality, length of hospitalisation, length of ventilation and oxygen dependence. Secondary outcome measures were pulmonary function and re-hospitalisations for recurrent breathing difficulties in subsequent years. Any adverse effects of the treatments were also noted, for example, hypersensitivity reactions.
DATA COLLECTION AND ANALYSIS
Data were extracted but cross-comparison was not possible due to the shortage of studies and lack of comparative measurements.
MAIN RESULTS
Four papers fitted the search criteria. None demonstrated statistically significant benefit of intravenous immunoglobulin (IVIG) treatment added to supportive care compared with supportive care alone. The evidence does not support a role for RSVIG in such a setting, with the doses used in the studies.
AUTHORS' CONCLUSIONS
The evidence on the role of respiratory syncytial virus immunoglobulin (RSVIG) in treating RSV severe infections is limited. Future research might consider using stronger titres of neutralising antibodies; and further analyse severely ill children (who might respond differentially compared to those less ill, but yet hospitalised).
Topics: Child; Humans; Immunoglobulins, Intravenous; Infant; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 20824840
DOI: 10.1002/14651858.CD004883.pub3