Efficacy Of Palivizumab Research Articles

50 New Analysis on the Cost-effectiveness of Palivizumab (PVZ) for the Prevention of Severe Respiratory Syncytial Virus (RSV) Infection in Canadian Infants Born 29-31 and 32-35 weeks’ Gestational Age (wGA)

Abstract Background PVZ remains the only licensed intervention to prevent severe RSV infection. The last formal cost-utility analysis (CUA) of its use in Canadian premature infants was published in 2010 (Smart J Med Econ 2010). Since then, the 3-variable International Risk Scoring tool (IRST) has been published (Blanken Pediatr Pulmonol 2018), which can guide prophylaxis for infants born 32-35 wGA at greatest risk of RSV hospitalization (RSVH). Objectives The objective of this study was to incorporate the IRST and non-hospitalized, medically-attended (emergency room/outpatient) RSV infections (MARI) into a CUA for the first time to provide an up-to-date economic evaluation of palivizumab versus no prophylaxis in Canadian 29-31 wGA and 32-35 wGA infants. Design/Methods Infants followed a semi-Markov process, having an RSVH, MARI, or being uninfected/non-medically attended. Hospitalized infants could be admitted to the intensive care unit (ICU; 17.9%) and ICU-admitted infants could die (0.43%). All surviving infants could experience respiratory morbidity up to 18 years, according to RSV infection and PVZ status. The RSVH rate in non-prophylaxed 29-31 wGA and moderate to high (MH) risk 32-35 wGA infants was 5.9% and 6.3%, respectively. PVZ reduced RSVH by 63.3% and 82.2% in 29-31 wGA and 32-35 wGA infants, respectively. PVZ costs (assuming 50 mg: CAN$752; 100 mg: $1,505) were calculated using Canadian birth statistics. The base case assumed all 29-31 wGA infants and MH-risk 32-35 wGA infants received PVZ, inclusion of indirect costs, no vial sharing, and a lifetime time horizon with 1.5% discounting. A cost per quality-adjusted life-year (QALY) of ≤$50,000 was considered cost-effective. Results PVZ prophylaxis resulted in a cost/QALY of $29,579 in 29-31 wGA infants and $27,951 in MH-risk 32-35 wGA infants versus no prophylaxis. In deterministic sensitivity analyses (±20% on main variables) the model was most sensitive to utility scores, PVZ cost, non-prophylaxed RSVH rate, and PVZ efficacy. Probabilistic sensitivity analyses (10,000 iterations) resulted in incremental costs of $30,857/QALY, with a 76.0% probability of cost-effectiveness at a $50,000 willingness-to-pay threshold for 29-31 wGA infants, and $28,167/QALY and 79.1% for MH-risk 32-35 wGA infants. Conclusion This new CUA, the first to incorporate the IRST and MARI, found that PVZ is highly cost-effective in Canadian 29-35 wGA infants (vs no prophylaxis) and has implications for prophylaxis policies in Canada. Potential competing interests Xavier Carbonell-Estrany and Bosco Paes have received research funding and/or compensation as advisor/lecturer from AbbVie and AstraZeneca. Jean-Eric Tarride has nothing to disclose. Barry Rodgers-Gray, Ian Keary and John Fullarton employers have received payment from AbbVie and AstraZeneca for work on various projects.

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29-35 weeks' gestational age.

Since the last Italian cost-utility assessment of palivizumab in 2009, new data on the burden of respiratory syncytial virus (RSV) and an International Risk Scoring Tool (IRST) have become available. The objective of this study was to provide an up-to-date cost-utility assessment of palivizumab versus no prophylaxis for the prevention of severe RSV infection in otherwise healthy Italian infants born at 29-31 weeks' gestational age (wGA) infants and those 32-35wGA infants categorized as either moderate- or high-risk of RSV-hospitalization (RSVH) by the IRST. A decision tree was constructed in which infants received palivizumab or no prophylaxis and then could experience: i) RSVH; ii) emergency room medically-attended RSV-infection (MARI); or, iii) remain uninfected/non-medically attended. RSVH cases that required intensive care unit admission could die (0.43%). Respiratory morbidity was considered in all surviving infants up to 18 years of age. Hospitalization rates were derived from Italian data combined with efficacy from the IMpact-RSV trial. Palivizumab costs were calculated from vial prices (50mg: €490.37 100mg: €814.34) and Italian birth statistics combined with a growth algorithm. A lifetime horizon and healthcare and societal costs were included. The incremental cost-utility ratio (ICUR) was €14814 per quality-adjusted life year (QALY) gained in the whole population (mean: €15430; probability of ICUR being <€40000: 0.90). The equivalent ICURs were €15139 per QALY gained (€15915; 0.89) for 29-31wGA infants and €14719 per QALY gained (€15230; 0.89) for 32-35wGA infants. The model was most sensitive to rates of long-term sequelae, utility scores, palivizumab cost, and palivizumab efficacy. Palivizumab remained cost-effective in all scenario analyses, including a scenario wherein RSVH infants received palivizumab without a reduction in long-term sequelae and experienced a 6-year duration of respiratory morbidity (ICUR: €27948 per QALY gained). In conclusion, palivizumab remains cost-effective versus no prophylaxis in otherwise healthy Italian preterm infants born 29-35wGA. The IRST can help guide cost-effective use of palivizumab in 32-35wGA infants.

Impact of using the International Risk Scoring Tool on the cost-utility of palivizumab for preventing severe respiratory syncytial virus infection in Canadian moderate-to-late preterm infants

Background and objectiveTo assess the cost-utility of palivizumab versus no prophylaxis in preventing severe respiratory syncytial virus (RSV) infection in Canadian moderate-to-late preterm (32–35 weeks’ gestational age) infants using an (i) International Risk Scoring Tool (IRST) and (ii) Canadian RST (CRST).MethodsA decision tree was developed to assess cost-utility. Infants assessed at moderate- and high-risk of RSV-related hospitalization (RSVH) by the IRST or CRST received palivizumab or no prophylaxis and then progressed to either (i) RSVH; (ii) emergency room/outpatient medically attended RSV-infection (MARI) or (iii) were uninfected/non-medically attended. Infants admitted to intensive care could incur mortality (0.43%). Respiratory morbidity was accounted in all uninfected surviving infants for 6 years or 18 years (RSVH/MARI). Palivizumab efficacy (72.2% RSVH reduction) and hospital outcomes were from the Canadian CARESS, PICNIC and RSV-Quebec studies. Palivizumab costs (50 mg: CAN$752; 100 mg: $1,505) were calculated from Canadian birth statistics combined with a growth algorithm. Healthcare/payer and societal costs (May 2022; 1.5% discounting) were included.ResultsCost per quality-adjusted life year (QALY) was $29,789 with the IRST (0.79 probability of being <$50,000) and $15,833 with the CRST (0.96 probability). The model was most sensitive to utility scores, long-term sequelae and palivizumab cost. Vial sharing improved the incremental cost-utility ratio (IRST: $22,319; CRST: $9,231).ConclusionsPalivizumab was highly cost-effective (vs no prophylaxis) in Canadian moderate-to-late preterm infants using either the IRST or CRST. The IRST has fewer risk factors than the CRST (3 vs 7, respectively), captures more potential RSVHs (85% vs 54%) and provides another option to guide cost-effective RSV prophylaxis in Canada.

Prophylaxis protects infants with congenital heart disease from severe forms of RSV infection: an Italian observational retrospective study

BackgroundIn children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality, requiring hospital admission and intensive care. The aim of the present study was to evaluate the effect of prophylaxis with palivizumab in preventing RSV-associated hospitalization in infants with CHD.MethodsWe carried out an observational, retrospective study in a paediatric cardiology division at a secondary-care centre in Italy, extracting from the database children with CHD who, from November 2004 to March 2022, matched the criteria for palivizumab prophylaxis, to evaluate the hospitalization rate in CHD patients with and without palivizumab prophylaxis and their RSV-related hospitalization characteristics compared with a group of children without CHD and no other underlying clinical conditions (control group, CG), hospitalized for RSV infection.ResultsOne hundred twenty-eight children with CHD were enrolled in the study, mainly (71.9%) with increased pulmonary flow, and received palivizumab prophylaxis. Twenty-seven received hospital care for bronchiolitis. Almost all CHD patients hospitalized for bronchiolitis (26 out of 27) received partial prophylaxis (≤ 3 doses). CHD patients with bronchiolitis stay longer in the hospital than control (14.4 ± 21.7 days vs 6.2 ± 2.3 days) some of which require intensive care (n = 4).ConclusionsOur study provides evidence of the efficacy of palivizumab in protecting patients with hemodynamically significant CHD under the age of 2 years from RSV disease and its life-threatening complications. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation.

Current State of Respiratory Syncytial Virus Disease and Management.

Respiratory syncytial virus (RSV) is a major cause of hospitalizations due to pneumonia and bronchiolitis. Substantial morbidity and socioeconomic burden are associated with RSV infection worldwide. Populations with higher susceptibility to developing severe RSV include premature infants, children with chronic lung disease of prematurity (CLDP) or congenital heart disease (CHD), elderly individuals aged > 65 years, and immunocompromised individuals. In the pediatric population, RSV can lead to long-term sequelae such as wheezing and asthma, which are associated with increased health care costs and reduced quality of life. Treatment for RSV is mainly supportive, and general preventive measures such as good hygiene and isolation are highly recommended. Although vaccine development for RSV has been a global priority, attempts to date have failed to yield a safe and effective product for clinical use. Currently, palivizumab is the only immunoprophylaxis (IP) available to prevent severe RSV in specific high-risk pediatric populations. Well-controlled, randomized clinical trials have established the efficacy of palivizumab in reducing RSV hospitalization (RSVH) in high-risk infants including moderate- to late-preterm infants. However, the American Academy of Pediatrics (AAP), in its 2014 policy, stopped recommending RSV IP use for ≥ 29 weeks’ gestational age infants. Revisions to the AAP policy for RSV IP have largely narrowed the proportion of pediatric patients eligible to receive RSV IP and have been associated with an increase in RSVH and morbidity. On the other hand, after reviewing the recent evidence on RSV burden, the National Perinatal Association, in its 2018 clinical practice guidelines, recommended RSV IP use for a wider pediatric population. As the AAP recommendations drive insurance reimbursements for RSV IP, they should be revised to help further mitigate RSV disease burden.

Utilization and efficacy of palivizumab for children with Down syndrome.

Palivizumab is a prophylactic drug used for severe respiratory syncytial virus (RSV) infection in young children with high-risk factors, such as prematurity and congenital heart diseases. Although Japan expanded the use of palivizumab for Down syndrome (DS) in 2013 regardless of additional high-risk factors, there is not enough evidence to support its use. We analyzed health insurance claim data from the JMDC (Tokyo, Japan) to investigate the prescription pattern and efficacy of palivizumab in children with DS. We enrolled children of ≤24months of age with DS at the start of the RSV epidemic season (2007-2015). We compared the risk of RSV-related admission with and without palivizumab prophylaxis using mixed effects logistic regression models accounting for patient-level clustering. Of 632 children, 30% (81/268) and 83% (303/364) received palivizumab before and after the expanded program (2007-2012 and 2013-2015), respectively. Among children with DS but without additional high-risk factors (n = 135), palivizumab use surged from 0% (0/62) to 73% (53/73). In the whole study population, RSV-related hospitalization occurred in 4.2% (16/384) patients with prophylaxis and 6.0% (15/248) patients without prophylaxis. The multivariate analysis revealed that palivizumab was associated with reduced RSV-related hospitalization (odds ratio: 0.41, 95% confidence interval: 0.18-0.92, P = 0.03). Virtually all children with DS in Japan have now received palivizumab, the use of which was associated with a reduction in RSV-related hospitalization in DS. Further evidence is required to clarify whether palivizumab prophylaxis should be risk-tailored or universal for DS.

Feasibility and ethical issues: experiences and concerns of healthcare workers regarding a new RSV prophylaxis programme in Nunavik, Quebec

ABSTRACT Background: The respiratory syncytial virus (RSV) is a major cause of hospitalisation in young Inuit children. Prophylaxis with palivizumab is routinely recommended for premature infants and those with severe pulmonary or cardiac diseases. In the fall 2016, the Quebec Ministry of Health expanded the criteria to include healthy full-term (HFT) newborns from Nunavik based on their high RSV hospitalisation rates. Objectives: The aim of this study was to describe the impact of this programme on Nunavik health services during the first RSV season after its implementation (2016–2017) by studying challenges, concerns and needs of healthcare workers (HCWs). Methods: An ethnographic approach was used. Semi-structured interviews focusing on HCWs experiences, and opinions to improve the new programme were conducted with 20 HCWs involved in its implementation. Results: Main reported challenges and concerns were: additional work(over)load, lack of information and evidence about the need and efficacy of palivizumab in HFT newborns, communication issues between stakeholders, and ethical issues regarding the Inuit population. Conclusion: The study revealed significant feasibility and acceptability issues. The programme was highly resource consuming. To address HCWs’ concerns, evidence-based data regarding palivizumab effectiveness in HFT infants, as well as consultation and involvement of Inuit population are warranted.

Respiratory syncytial virus (RSV) infection in children with medical complexity.

Children with medical complexity (CMC) are vulnerable to respiratory illness hospitalization (RIH) and respiratory syncytial virus (RSV)-related hospitalization (RSVH) due to multisystem disorders and compromised airways. It is unknown whether RSV prophylaxis is effective, or if RSVH is associated with significant morbidities in CMC. The study objectives were to (1) determine the incidence of RSV-related infection in prophylaxed CMC during the first 3years of life and (2) assess the burden of illness following RSVH. A single tertiary center, retrospective study, was conducted of CMC who received palivizumab during the 2012-2016 RSV seasons. Fifty-four subjects were enrolled; most received one (38.9%, n= 21) or two (57.4%, n= 31) seasons of prophylaxis (mean= 4.2 [SD = 1.24], palivizumab doses per season). The cohort comprised children with multiple medical conditions (n= 22, 40.8%), tracheostomy (n= 18, 33.3%), and invasive (n= 10, 18.5%) or non-invasive (n= 4, 7.4%) ventilation. Of the CMC, 24 were hospitalized 47 times for a viral-related respiratory illness. RSV incidence in the first 3years of life was 7.4%. Viral-related RIH and RSVH rates were 44.4% (n= 24/54) and 1.9% (n= 1/54), respectively. Of the four RSV-positive children, one was ventilated for 9days, two acquired nosocomial RSV that was managed on the ward, and one was discharged home under close complex care supervision. All four RSV-positive cases required additional oxygen during their illness. CMC experience a high viral-related RIH rate and palivizumab likely minimizes RSV-related events and associated morbidities. The efficacy of palivizumab in CMC, especially in those ≤ 3years, should be prospectively evaluated.

Respiratory syncytial virus prophylaxis and the "special population".

Bronchiolitis is the most frequent airway infection in the first 2 years of life, and the respiratory syncytial virus (RSV) is the most frequently responsible virus. In selected high-risk groups, RSV may cause severe respiratory disease leading to hospitalization, need for mechanical ventilation, and even death. These high-risk groups include children with congenital heart disease, infants with neuromuscular impairment, cystic fibrosis, Down Syndrome, immunodeficiency syndromes and others specific conditions. In these high-risk populations defined in literature as "special population", a 3- to 10-fold increase in the rate of RSV hospitalization has been observed, justifying RSV specific prophylaxis with palivizumab, a monoclonal antibody that binds a viral glycoprotein epitope and blocks the link between RSV and target cell. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomized clinical trials are not feasible. The purpose of this paper is to give an update from the literature of various conditions at higher risk to develop severe RSV infection, and to offer an overview of the efficacy of palivizumab in preventing RSV infection in these specific populations.

Alternative Viewpoint: Efficacy and Effectiveness of Respiratory Syncytial Virus Immunoprophylaxis in Children with Cystic Fibrosis - An Unsolved Question with More to Be Asked.

The systematic review of the safety and efficacy of palivizumab in children with cystic fibrosis (CF) by Kua and Lee1 demonstrates the woeful lack of definitive data in this area and correctly points out the critical need for additional well-designed studies. Their review examined 10 scientific reports and concluded that respiratory syncytial virus (RSV) immunoprophylaxis “may have a potential role in reducing RSV hospitalizations in children aged less than 2 years with CF”.1 While we fully agree with the authors’ non-committal conclusions, it is important to highlight the extreme caution that must be exercised in interpreting this literature. This article is protected by copyright. All rights reserved.

Systematic Review of the Safety and Efficacy of Palivizumab among Infants and Young Children with Cystic Fibrosis.

Respiratory syncytial virus (RSV) is a common pathogen in infants with cystic fibrosis (CF). The use of palivizumab prophylaxis for RSV infection as the standard of care for infants with CF remains controversial. To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years. Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis. The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880). Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF.

Respiratory syncytial virus associated hospitalizations in preterm infants of 29 to 32\xa0weeks gestational age using a risk score tool for palivizumab prophylaxis

To evaluate the efficacy of palivizumab in infants of 29 to 32 weeks of gestational age (GA) based on a risk score tool developed for Austria. Retrospective single-center cohort study including all preterm infants of 29 (+0) to 32 (+6) weeks of GA born between 2004 and 2012 at a tertiary care university hospital. Data on RSV-related hospitalizations over the first 2 years of life were analyzed and compared between those having received palivizumab and those without. The study population was comprised of 789 of 816 screened infants, of whom 262 (33%) had received palivizumab and 527 (67%) had not. Nine of 107 rehospitalizations (8.4%) in the palivizumab group compared to 32 of 156 rehospitalizations (20.5%) in the group without prophylaxis were tested RSV-positive (p = 0.004; OR 0.356 [CI 90% 0.184–0.689]). Proven and calculated RSV hospitalization rate was 3.1% (8/262) in the palivizumab group and 5.9% (31/527) in the group without (p = 0.042; OR 0.504 [CI 90% 0.259–0.981]). Increasing number of risk factors (up to three) increased the RSV hospitalization rate in infants with (6.1%) and without (9.0%) prophylaxis. RSV-associated hospitalizations did not differ between groups with regard to length of stay, severity of infection, age at hospitalization, demand of supplemental oxygen, need for mechanical ventilation, and admission rate to the ICU. A risk score tool developed for infants of 29 to 32 weeks of gestational age led to a reduction of RSV-associated hospitalizations without influencing the severity of disease.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

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. 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. 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. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. 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. 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.

Retrospective Evaluation of Palivizumab Efficacy and Safety for RSV Prophylaxis in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Retrospective Evaluation of Palivizumab Efficacy and Safety for RSV Prophylaxis in Pediatric Hematopoietic Stem Cell Transplant Patients: A Single Center Experience

Modeling the Potential Impact of the 2014 American Academy of Pediatrics Respiratory Syncytial Virus Prophylaxis Guidance on Preterm Infant RSV Outcomes.

IntroductionThe American Academy of Pediatrics (AAP) Committee on Infectious Diseases issued updated guidance on respiratory syncytial virus (RSV) prophylaxis in 2014. This report models the potential impact of the new guidance on RSV outcomes in preterm infants 29–34 weeks’ gestational age (wGA) without chronic lung disease in the United States.MethodsThe number of preterm infants was estimated using 2012 natality data. Palivizumab utilization prior to the 2014 guidance update was estimated using 2013–2014 specialty pharmacy utilization data. Low, moderate, and high RSV hospitalization (RSVH) rates as well as average hospital length of stay, intensive care unit (ICU) admissions and mechanical ventilation (MV) frequencies were derived from published observational studies. Palivizumab efficacy was derived from two randomized clinical trials. RSV events that would be attributable to the 2014 guidance change were calculated for preterm infants 29–31 and 32–34 wGA.ResultsAnnual number of infants 29–34 wGA surviving the neonatal period was estimated at 123,687. Of these, an estimated 44,712 (37%) would receive palivizumab based on the 2012 guidance. The annual number of RSVH among infants 29–34 wGA would increase from 3580 under the 2012 guidance to 6166 under the 2014 guidance based on moderate rates. This would result in an additional 24,440 hospitalization days, 1162 ICU admissions, and 584 MV events among this population.ConclusionsBased on published historical and contemporary data on RSVH rates in preterm infants 29–34 wGA, the 2014 AAP guidance is expected to result in additional burden to the healthcare system and families of preterm infants. The impact of the new guidance will be difficult to detect among the overall infant population, particularly in settings without routine testing for RSV, but the impact will be substantial for the small high-risk population affected by the changes.FundingAstraZeneca.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-015-0097-3) contains supplementary material, which is available to authorized users.

Safety and Effectiveness of Palivizumab in Children at High Risk of Serious Disease Due to Respiratory Syncytial Virus Infection: A Systematic Review.

IntroductionLower 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.MethodsWe 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.ResultsThe 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.ConclusionRates 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0046-6) contains supplementary material, which is available to authorized users.

A population-weighted, condition-adjusted estimate of palivizumab efficacy in preventing RSV-related hospitalizations among US high-risk children

Preterm infants ≤ 35 weeks' gestational age (GA), and children ≤ 24 months of age with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital heart disease (hsCHD) are at high risk for developing severe respiratory syncytial virus (RSV) disease. In 3 previous randomized, placebo-controlled trials, palivizumab efficacy varied significantly based on these underlying conditions, and trial enrollment was not proportional to condition prevalence. This analysis provides the first estimate of the population-weighted efficacy of palivizumab in high-risk children, adjusting for condition prevalence. Palivizumab efficacy by high-risk condition was obtained from the clinical trials. The annual number of US children with each condition was obtained from the 2010 Centers for Disease Control and Prevention (CDC) natality statistics and the medical literature. Data from specialty pharmacies in the US palivizumab distribution network were used to estimate the population for each condition receiving at least 1 dose in the outpatient setting in 2012–2013. The weighted efficacy estimate was derived by summing the products of the condition-specific relative risk reductions and the relative frequency of each condition among those receiving palivizumab. The US population-weighted efficacy estimate for those receiving palivizumab was 68%. Due to the low prevalence of BPD and hsCHD and the higher efficacy observed in preterm infants without BPD or CHD, the population-weighted estimate of palivizumab efficacy is higher than the overall 45–55% efficacy observed in initial clinical trials. Consistent with 2012 American Academy of Pediatrics RSV prophylaxis recommendations, a low proportion of preterm infants 32–35 weeks' gestational age receive palivizumab.

Respiratory syncytial virus-related hospitalization in premature infants without bronchopulmonary dysplasia: subgroup efficacy analysis of the IMpact-RSV trial by gestational age group

Respiratory syncytial virus-related hospitalization in premature infants without bronchopulmonary dysplasia: subgroup efficacy analysis of the IMpact-RSV trial by gestational age group Gerard Notario,1 Pamela Vo,2 Katherine Gooch,2 Roger Deaton,3 Xionghua Wu,4 Brian Harris,4 Parthiv J Mahadevia,4 Pablo J S&aacute;nchez51Clinical Development and Medical Affairs, 2Global Heath Economics and Outcomes Research, 3Statistics, AbbVie Inc., North Chicago, IL, 4MedImmune, LLC, Gaithersburg, MD, 5The Research Institute at Nationwide Children&#39;s Hospital, The Ohio State University, Columbus, OH, USABackground: Respiratory syncytial virus (RSV) infections are common during childhood and are a major cause of hospitalization resulting from serious lower respiratory tract infections. Palivizumab is approved for prevention of serious lower respiratory tract disease caused by RSV infection in infants and young children at high risk of RSV disease. Although the previously published IMpact-RSV trial included the overall results for palivizumab prophylaxis in a cohort of premature infants who did not have bronchopulmonary dysplasia (BPD), there is an ongoing demand to understand the efficacy of palivizumab in premature infants without BPD by gestational age group.Methods: This post hoc analysis assesses IMpact-RSV trial data within eleven gestational age groups for the cohort of 724 premature infants who were &le;6 months of age and did not have BPD. RSV-related hospitalization rates along with corresponding 95% exact binomial confidence intervals were determined for these specific gestational age groups. Relative reductions in risk of RSV-related hospitalizations for palivizumab versus placebo with corresponding 95% confidence intervals were also calculated.Results: Analysis of a cohort of premature infants without BPD from the IMpact-RSV trial revealed that palivizumab consistently reduced RSV-related hospitalizations (64.5%&ndash;100%) versus placebo in all eleven gestational age groups evaluated. Palivizumab significantly decreased the relative risk of RSV-related hospitalization (73%&ndash;82%, P&lt;0.05) versus placebo in the 28&ndash;31, 29&ndash;32, 29&ndash;33, 32&ndash;34, and 32&ndash;35 gestational week age groups. Relative reductions in risk for RSV-related hospitalizations were substantial for the moderate/late preterm groups (82% for both the 32&ndash;34 and 32&ndash;35 gestational week age groups).Conclusion: Palivizumab effectively reduced RSV-related hospitalization rates in premature infants without BPD across all gestational age groups evaluated. In particular, reductions in RSV-related hospitalizations were substantial for the moderate/late preterm groups (32&ndash;34 and 32&ndash;35 gestational weeks).Keywords: respiratory syncytial virus, bronchopulmonary dysplasia, palivizumab, gestational age, prophylaxis

Glycan variants of a respiratory syncytial virus antibody with enhanced effector function and in vivo efficacy.

Respiratory syncytial virus (RSV) can cause devastating lower respiratory tract infections in preterm infants or when other serious health problems are present. Immunoprophylaxis with palivizumab (Synagis), a humanized IgG1 mAb, is the current standard of care for preventing RSV infection in at-risk neonates. We have explored the contribution of effector function to palivizumab efficacy using a plant-based expression system to produce palivizumab N-glycan structure variants with high homogeneity on different antibody isotypes. We compared these isotype and N-glycoform variants with commercially available palivizumab with respect to both in vitro receptor and C1q binding and in vivo efficacy. Whereas the affinity for antigen and neutralization activity of each variant were indistinguishable from those of palivizumab, their Fcγ receptor binding profiles were very different, which was reflected in either a reduced or enhanced ability to influence the RSV lung titer in challenged cotton rats. Enhanced Fcγ receptor binding was associated with reduced viral lung titers compared with palivizumab, whereas abrogation of receptor binding led to a drastic reduction in efficacy. The results support the hypotheses that classic antibody neutralization is a minor component of efficacy by palivizumab in the cotton rat and that antibody-dependent cell-mediated cytotoxicity activity can significantly enhance the efficacy of this antiviral mAb.

Is palivizumab effective as a prophylaxis of respiratory syncytial virus infections in cystic fibrosis patients? A meta-analysis

BackgroundInfections by respiratory syncytial virus (RSV) are more severe in patients with cystic fibrosis (CF), and many CF units use palivizumab as prophylaxis; however, information about palivizumab efficacy in CF patients is almost lacking. MethodsA literature search up to December 2012 on the morbidity of RSV bronchiolitis in CF patients and on the safety and efficacy of palivizumab in those patients was performed. A random-effects meta-analysis was conducted for those studies meeting pre-specified search criteria. Historical controls were allowed. ResultsThe number of patients who received palivizumab was 354 and the hospital admission rate was 0.018 (95% CI 0.0077–0.048). The corresponding number in the non-treated groups was 463 patients with an admission rate of 0.126 (95% CI 0.086–0.182) (Q=13.9; p<0.001). ConclusionPalivizumab may have a role in the prevention of severe lower airway infection by RSV in CF patients.