-
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 -
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 -
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 -
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 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 -
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 -
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 -
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 -
The Cochrane Database of Systematic... Aug 2019Millions of children are hospitalised due to respiratory syncytial virus (RSV) infection every year. Treatment is supportive, and current therapies (e.g. inhaled...
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 is sometimes 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 licenced 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. OBJECTIVES: To assess the effects of immunoglobulins for the treatment of RSV-proven lower respiratory tract infections in children aged up to three years, admitted to hospital. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE, Embase, CINAHL, and Web of Science (from inception to 6 November 2018) with no restrictions. We searched two trial registries for ongoing trials (to 30 March 2018) 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 quality using GRADE.
MAIN RESULTS
We included seven trials involving 486 infants and children aged up to three years. The immunoglobulin preparations used in these trials included anti-RSV immunoglobulin and the monoclonal antibody preparations palivizumab and motavizumab. We assessed the primary outcomes of mortality, length of hospital stay, and adverse events as providing low- or very low-certainty evidence due to risk of bias and imprecision. All trials were conducted at sites in high-income countries (USA, Chile, New Zealand, Australia), with two studies including a site in a middle-income country (Panama). Five of the seven studies were "supported" or "sponsored" by the trial drug manufacturers. We found no evidence of a difference between immunoglobulins and placebo for mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.14 to 5.27; 3 trials; 196 children; 4 deaths; 2 deaths amongst 98 children receiving immunoglobulins, and 2 deaths 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), and length of hospitalisation (mean difference -0.70, 95% CI -1.83 to 0.42; 5 trials; 324 children; low-certainty evidence). There was no evidence of a difference between immunoglobulins and placebo in adverse events of any severity or seriousness (reported in five trials) or serious adverse events (four trials) (RR for any severity 1.18, 95% CI 0.78 to 1.78; 340 children; low-certainty evidence, and for serious adverse events 1.08, 95% CI 0.65 to 1.79; 238 children; low-certainty evidence).We found no evidence of a significant difference between immunoglobulins and placebo for any of our secondary outcomes. We identified one ongoing trial.
AUTHORS' CONCLUSIONS
We found insufficient evidence of a difference between immunoglobulins and placebo for any review outcomes. We assessed the evidence for the effects of immunoglobulins when used as a treatment for RSV lower respiratory tract infection in hospitalised infants and young children as of low or very low certainty due to risk of bias and imprecision. We are uncertain of the effects of immunoglobulins on these outcomes, and the true effect may be substantially different from the effects reported 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: Antibodies, Monoclonal, Humanized; Antiviral Agents; Child; Child, Preschool; Hospitalization; Humans; Immunoglobulins, Intravenous; Infant; Infant, Newborn; Length of Stay; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 31446622
DOI: 10.1002/14651858.CD009417.pub2 -
The Cochrane Database of Systematic... Jul 2016Respiratory 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. This is an update of a previously published review.
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: 05 May 2016.
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: Antiviral Agents; Cystic Fibrosis; Drug Administration Schedule; Humans; Infant; Palivizumab; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Syncytial Virus Infections
PubMed: 27439110
DOI: 10.1002/14651858.CD007743.pub6