RSV-related Hospitalization Rates Research Articles

Risk of RSV-related hospitalization is associated with gestational age in preterm (born at 29–34 wGA) infants without outpatient palivizumab administration

ABSTRACT Palivizumab has been shown to decrease RSV-related hospitalization (RSVH) risk and reduce RSVH severity. American Academy of Pediatrics (AAP) guidance on administration of palivizumab has changed over time; in 2014, palivizumab was no longer recommended in preterm infants born at 29 weeks gestational age (wGA) or later. This study’s objective was to describe RSVH risk and severity in preterm infants (29–34 wGA) without comorbidities relative to healthy term infants and to each other by gestational age. Using the MarketScan Multi-State Medicaid and Commercial Databases, infants born from July 1, 2014 to June 30, 2019, at 29–34 wGA (preterm) and >37 wGA (term) were identified. During RSV seasons (November to March) from 2014 to 2020, claims incurred by infants while they were <6 months old were evaluated for RSVH and RSVH characteristics. This study included 63,351 preterm infants and 1,076,389 term infants without outpatient palivizumab administration. Rate of RSVH was higher in infants with lower wGA at birth and ranged 3.32–5.72 per 100 infant-seasons in Medicaid-insured infants and 3.21–4.84 in commercially insured infants. Relative risk of RSVH was 5–8 times higher in Medicaid-insured preterm infants and 3–5 times higher in commercially insured preterm infants compared to term infants. ICU admissions and mechanical ventilation were more common during RSVH in preterm infants relative to term infants. RSV-related outpatient healthcare utilization was also 2–3 times higher in preterm infants born at 31–34 wGA. Increased utilization of palivizumab among infants born at 29–34 wGA may decrease RSVH rates and result in less severe course in preterm infants with RSVH.

Effectiveness and Safety of Palivizumab for the Prevention of Serious Lower Respiratory Tract Infection Caused by Respiratory Syncytial Virus: A Systematic Review.

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. 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). 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. This systematic review supports the effectiveness and safety of palivizumab in the indicated populations. · 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..

The burden of respiratory syncytial virus infections among children with sickle cell disease.

Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. We conducted a retrospective, nested, case-control study of children with SCD <18years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5years and 5-18years, respectively. The RSV-related hospitalization rate for children <5years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8years vs 7.6years, P<.001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

DOES PRESENCE OF DOWN SYNDROME INCREASE RESPIRATORY SYNCYTIAL VIRUS (RSV) RELATED HOSPITALIZATION IN CHILDREN LESS THAN 2 YEARS OF AGE? A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND Down syndrome (DS) is associated with a number of immunologic abnormalities and congenital heart disease (CHD) which increase susceptibility to respiratory syncytial virus (RSV). However current position statements from the American Academy of Pediatrics and the Canadian Paediatric Society do not recommend routine RSV prophylaxis with Palivizumab to all infants with DS, OBJECTIVES To conduct a systematic reviewand meta-analysis of observational studies to compare RSV-related hospitalization (RSVH) rates, length of hospital stay(LOS), need for intensive care and assisted ventilation in DS children &lt;2 years of age compared with children without DS. DESIGN/METHODS Data Sources: The authors searched MEDLINE, Embase, CINAHL, reference lists of relevant articles, abstracts and conference proceedings, results of unpublished trials, and contacted the primary authors of relevant studies. Studies were included if data was provided on RSV-related hospitalization in children &lt;2yr of age with and without DS. Data extraction &amp; Synthesis: Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality using the Newcastle-Ottawa Scale. Data was extracted and checked in duplicate. Main outcomes &amp; measures: The primary outcome was RSV-related hospitalization. Secondary outcomes included length of hospital stay, need for intensive care and assisted ventilation. Sensitivity analysis was conducted for the primary outcome comparing DS infants without congenital heart disease (CHD) with non-DS infants. RESULTS 19 cohort studies met the inclusion criteria. Ten studies involving 1,390,380 children were analyzed. DS-children had significantly higher RSVH compared to non-DS children (Relative Risk, 6.97; 95% CI, 6.01 to 8.08; I2=0%; Figure 1a). Among children hospitalized with RSV, need for assisted ventilation (RR, 5.82; 95% CI, 1.81 to 18.69; I2=84%; Figure 1b) and LOS (Mean difference, 2.28 days; 95% CI, 1.61 to 2.96 days; I2=0%; Figure 1c) were significantly higher in DS-children. The sensitivity analysis also confirmed that DS children without CHD had a significantly higher RSVH rate compared to non-DS children (RR, 6.31; 95% CI, 4.83 to 8.23;I2=0%; Figure 1d). CONCLUSION Compared to children without DS, RSV-related hospitalization, need for assisted ventilation and length of RSV-related hospital stay is significantly higher in children with DS in the first 2 years of life. The results of this systematic review should prompt a favorable recommendation for routine RSV prophylaxis in both healthy and medically compromised DS children aged &lt;2years.

Use of Palivizumab in Germany - Report from the German Synagis™ Registry 2009 - 2016.

Following national recommendations, palivizumab is administered in Germany to high-risk infants to prevent hospitalizations related to Respiratory Syncytial Virus infection. In this post marketing observational study (German SYNAGIS™ Registry) data on risk factors and the clinical course of children, who received at least one palivizumab injection between 2009-2016 (01 September to June 30) were entered into an internet-based data entry system by the attending physicians after informed consent. 63 572 immunizations were documented for 12 729 evaluable patients (EVP) from 2009 to 2016, with an average of 5.0 immunizations per patient per season. 45% of infants received more than 5 injections. The predominant primary reason for immunization was premature birth (74%). In the EVP the rate of hospitalizations with causal relationship to RSV was 0.7% (=92/12 729) or 1.2% in a worst case scenario including patients with missing RSV test. In patients with hemodynamically significant congenital heart disease as main indication, RSV-related hospitalization rate was 0.8%. Intensive care was necessary in 16.9% (median duration 3 days), mechanical ventilation in 8.0%. No death related to RSV infection was reported. Keeping in mind the limitations of an uncontrolled prospective observational study, our results confirm the effectiveness and safety of palivizumab prophylaxis. The total number of patients with hsCHD is lower than expected. A better adjustment to the regional epidemiology would probably reduce the need for more than 5 injections.

Palivizumab use in infants with Down syndrome-report from the German Synagis™ Registry 2009-2016.

Data from 249 children with DS receiving palivizumab prophylaxis in seven consecutive RSV seasons (2009-2016) in Germany reveal important differences between patients with and without DS concerning the main indication for palivizumab use and additional risk factors. Bearing in mind the limitations of an uncontrolled postmarketing observational study, the results confirm the field effectiveness of palivizumab prophylaxis in this special population. What is Known: • Recent studies describe the Down syndrome as independent risk factor for a complicated clinical course in infants with RSV infection. What is New: • Compared with other infants receiving palivizumab prophylaxis, patients with Down syndrome significantly more often had congenital heart disease, siblings in kindergarten or school, treatment with oxygen at home, immunodeficiency, and neuromuscular impairment. • In infants with palivizumab prophylaxis breakthrough, RSV-related hospitalization rates were not significantly higher in those with Down syndrome.

Respiratory Syncytial Virus Infection-associated Hospitalization Rates in Infants and Children With Cystic Fibrosis.

Infections with respiratory syncytial virus (RSV) are the leading cause for hospital admissions in infants and young children. The incidence of RSV-related hospitalizations in patients with cystic fibrosis (CF) is unclear. To date, no effective treatment for RSV infections is available. Thus, prophylaxis with the monoclonal antibody palivizumab is an important option. In a retrospective, single-center study at the Department of Pediatrics and Adolescent Medicine of the Medical University Graz, Austria, we analyzed all CF patients born between 1995 and 2012, who were admitted for respiratory problems between 1995 and 2014. We also defined a group of hypothetical RSV infections with the following criteria: admission caused by a respiratory infection during the first RSV season of life when no test for RSV was performed. Furthermore, we assessed the effectiveness of palivizumab as a prevention of RSV-related hospitalizations. A total of 51 patients with CF were identified. The RSV-related hospitalization rate for the first RSV season was 0. Two patients (3.9%) were hospitalized 3 and 4 times, respectively, caused by RSV infections. The mean age at the time of admission was 12.4 ± 2.5 years. One case (1.9%) met our criteria for hypothetical RSV infections. There was no difference in RSV-related hospitalization rates between patients who received palivizumab and those who did not. We found a low rate of RSV-related hospitalizations and could not demonstrate a benefit of palivizumab prophylaxis regarding a decrease of RSV-related hospital admissions. The role of RSV reinfections in CF patients beyond infancy appears to be underestimated.

Comparing First- and Second-Season Palivizumab Prophylaxis in Patients with Hemodynamically Significant Congenital Heart Disease (HSCHD) in the ‘Caress’ Database (2005-2014)

Abstract BACKGROUND: Compared with normal children, RSV-related hospi-talization (RSVH) rates in children with HSCHD are 2-4 fold higher even up to 2 years of age with an overall weighted mean mortality rate of 5.2%. Pediatric advisory guidelines recommend prophylaxis against respiratory syncytial virus (RSV) for infants with HSCHD. However, current recommendations cast doubt as to whether prophylaxis is beneficial beyond 1 year of age. OBJECTIVES: To determine whether there are differences in RSVH in HSCHD infants receiving palivizumab during the first versus second RSV season in the Canadian Registry of palivizumab (CARESS). DESIGN/METHODS: CARESS is a prospective registry of infants who received ≥1 dose of palivizumab at one of 32 sites across Canada during the 2005-2014 RSV seasons. Demographic data were collected at enrollment and respiratory-illness-related hospitalization events recorded monthly. In the event of a hospitalization, the relevant hospital records were reviewed by the site’s research nurse for detailed information on criteria for hospital-ization, length of stay (regular ward vs. ICU), days on respiratory support and/or intubation, and RSV test type and diagnosis. Infants aged &amp;lt;24 months with cyanotic or acyanotic HSCHD were recruited. RESULTS: 1306 (64.9%) of 2013 infants received prophylaxis only for the first season. 707 (35.1%) were prophylaxed during the second season (average age in months: 4.7 [first season] vs 14.7 [second season]). Baseline demographics for both seasons were similar. However, infants aged &amp;gt;1year had a more complicated neonatal course, with significantly longer neonatal length of stay (46.7 versus 25.6 days). Infants received: 4.5±1.4 injections; 90.5% of their expected injections and 88.2% of their injections within the appropriate time intervals. 26 infants in the first year (RSVH rate: 2.26%) and 11 infants in the second year (RSVH rate: 2.09%) were hospitalized. Cox regression analysis showed no significant differences in hazards between infants in their first or second year of prophylaxis in the time to first RSVH (Hazard ratio: 1.4, 95%CI 0.5-4.0, p=0.52) CONCLUSION: Infants enrolled in the CARESS database in the second RSV season had a similar hazard of RSVH as those in the first year of life. These findings suggest that infants aged &amp;gt;1 year with HSCHD who remain unstable, are equally at risk for RSVH and merit palivizumab prophylaxis.

Effectiveness of palivizumab in children with childhood interstitial lung disease: The French experience.

There is a lack of evidence concerning the effectiveness of immunoprophylaxis with palivizumab in children with childhood interstitial lung disease (chILD). In this retrospective study, we evaluated the effectiveness of palivizumab for decreasing the rate of RSV-related hospitalizations in children under the age of 24 months with chILD treated with corticosteroids. A retrospective national study was conducted in France. Patients born between 2007 and 2013, diagnosed with chILD and on corticosteroid treatment were identified through the French online database for pediatric interstitial lung disease (Respirare(®) ). Data were collected for the etiology and severity of chILD, risk factors and preventive measures for bronchiolitis, palivizumab immunoprophylaxis, and hospitalizations for bronchiolitis and RSV-bronchiolitis. We included and evaluated 24 children during their first two RSV seasons, corresponding to 36 patient-seasons. The observed rate of RSV-related hospitalization (305/1000 patient-seasons), and the median length of stay (7 days), were higher than those for the general population. RSV-related hospitalization rates did not differ significantly between children with and without palivizumab prophylaxis (5/16 vs. 4/18, respectively, P = 0.70). Children with chILD on corticosteroid treatment are at high risk of hospitalization for RSV-bronchiolitis, which tends to be more severe in these children than in the general population. The effectiveness of palivizumab prophylaxis in this population remains to be demonstrated. Pediatr Pulmonol. 2016;51:688-695. © 2015 Wiley Periodicals, Inc.

Partial palivizumab prophylaxis and increased risk of hospitalization due to respiratory syncytial virus in a Medicaid population: a retrospective cohort analysis.

BackgroundInfection with respiratory syncytial virus (RSV) is common among young children insured through Medicaid in the United States. Complete and timely dosing with palivizumab is associated with lower risk of RSV-related hospitalizations, but up to 60% of infants who receive palivizumab in Medicaid population do not receive full prophylaxis. The purpose of this study was to evaluate the association of partial palivizumab prophylaxis with the risk of RSV hospitalization among high-risk Medicaid-insured infants.MethodsClaims data from 12 states during 6 RSV seasons (October 1st to April 30th in the first year of life in 2003–2009) were analyzed. Inclusion criteria were birth hospital discharge before October 1st, continuous insurance eligibility from birth through April 30th, ≥ one palivizumab administration from August 1st to end of season, and high-risk status (≤34 weeks gestational age or chronic lung disease of prematurity [CLDP] or hemodynamically significant congenital heart disease [CHD]). Fully prophylaxed infants received the first palivizumab dose by November 30th with no gaps >35 days up to the first RSV-related hospitalization or end of follow-up. All other infants were categorized as partially prophylaxed.ResultsOf the 8,443 high-risk infants evaluated, 67% (5,615) received partial prophylaxis. Partially prophylaxed infants were more likely to have RSV-related hospitalization than fully prophylaxed infants (11.7% versus 7.9%, p< 0.001). RSV-related hospitalization rates ranged from 8.5% to 24.8% in premature, CHD, and CLDP infants with partial prophylaxis. After adjusting for potential confounders, logistic regression showed that partially prophylaxed infants had a 21% greater odds of hospitalization compared with fully prophylaxed infants (odds ratio 1.21, 95% confidence interval 1.09-1.34).ConclusionsRSV-related hospitalization rates were significantly higher in high-risk Medicaid infants with partial palivizumab prophylaxis compared with fully prophylaxed infants. These findings suggest that reduced and/or delayed dosing is less effective.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2431-14-261) 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.

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

Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005-2012) compared to other international registries.

Respiratory syncytial virus (RSV) infection occurs commonly in infants aged ≤2 years, and severe infection results in hospitalization with accompanying morbidity and mortality. Palivizumab has been available for prophylaxis for the past 15 years. Prospective data on patients who received palivizumab from 2005 to 2012 has been assembled in the Canadian registry (CARESS) to document utilization, compliance, and health outcomes in both hospital and community settings. Long-term data is necessary to evaluate the impact of palivizumab on the incidence of RSV infections, minimize healthcare resources, and identify which infant subpopulations are receiving prophylaxis. A database search was also conducted for similar information from published registries, and hospitalization rates were compared to results from randomized clinical trials (RCTs).Overall hospitalization rates (percent; range) for respiratory-related illnesses and RSV-specific infection in infants who meet standard indications for prophylaxis were 6.6 (3.3–7.7) and 1.55 (0.3–2.06), respectively, in CARESS, which closely aligns with registry data from 4 other countries, despite the former comprising the largest cohort of complex patients internationally. Overall RSV-related hospitalization rates were lower across registries compared to equivalent patients in RCTs. Registry data provides valuable information regarding real-world experience with palivizumab, while facilitating the genesis of new research themes.

Managing the Morbidity Associated with Respiratory Viral Infections in Children with Congenital Heart Disease

Children with congenital heart disease (CHD) are at risk for increased morbidity from viral lower respiratory tract infections because of anatomical cardiac lesions than can worsen an already compromised respiratory status. Respiratory syncytial virus (RSV) remains an important pathogen in contributing toward the morbidity in this population. Although the acute treatment of RSV largely remains supportive, the development of monoclonal antibodies, such as palivuzumab, has reduced the RSV-related hospitalization rate in children with CHD. This review highlights the specific cardiac complications of RSV infection, the acute treatment of bronchiolitis in patients with CHD, and the search for new therapies against RSV, including an effective vaccine, because of the high cost associated with immunoprophylaxis and its lack of reducing RSV-related mortality.

Description of the outcomes of prior authorization of palivizumab for prevention of respiratory syncytial virus infection in a managed care organization.

Respiratory syncytial virus (RSV) is the leading cause of upper and lower respiratory tract infections in infants and young children. Most children are exposed to the virus before they are 2 years old and experience such symptoms as cough, fever, and irritability. In a select population of infants, the virus can cause hypoxemia and hospitalization. To avoid hospitalization, good infection control practices should be employed, and for those infants at high risk, prophylaxis with palivizumab is indicated. Palivizumab has been shown to reduce hospitalization rates in high-risk infants by 50%. Because of the high cost of palivizumab, it is prudent to use this medication in the population in which it will be most effective. The American Academy of Pediatrics (AAP) established the criteria for those infants who would benefit the most from palivizumab prophylaxis, and these criteria were the foundation for a prior authorization (PA) program to determine coverage of palivizumab in a health plan of approximately 500,000 members. To (a) analyze the appropriateness of this PA program for palivizumab used prophylactically for RSV, and (b) determine the financial cost associated with the medication and disease for this health plan. A 3-year, retrospective study was conducted from the 2005- 2006 RSV season through the 2007-2008 season. The primary endpoint outcome was the hospitalization rate associated with RSV infection. Secondary endpoints included the cost of palivizumab and RSV-related emergency room (ER) utilization. Infants were placed into 2 groups: those who received PA approval for use of palivizumab and those who were denied coverage in the PA process. Disease-related hospitalization and ER visits were identified by at least 1 administrative claim containing either a primary or secondary ICD-9-CM code for any of the following: RSV (079.6), acute bronchiolitis caused by RSV (466.11), or pneumonia caused by RSV (480.1). Drug cost was defined as the health plan's allowed amount, which is based on a predefined fee schedule for the Current Procedural Terminology (CPT) code 90378 for palivizumab. Hospital and ER costs are the health plan allowed amounts (health plan plus member cost) based on the reimbursement rates determined by diagnosis related group (DRG) and other coding, and the plan-allowed amount based on DRGs includes all services and drugs provided in the specific encounter. Drug cost avoided was calculated as the average cost of palivizumab treatment per episode multiplied by the number of infants denied coverage of palivizumab over the 3-year study period. Over 3 RSV seasons through May 2008, the PA program received 1,090 requests for coverage of palivizumab, of which 348 (31.9%) were denied. Of 742 PA-approved infants, 629 received at least 1 dose of palivizumab. The mean (SD) gestational age of the PA-denied group was 34.4 (2.5) weeks versus 32.5 (4.0) weeks for the PA-approved group (P < 0.001). In the PA-denied group, 14 infants (4.0%) were subsequently hospitalized with an RSV infection, and 5 (1.4%) had an RSV-related ER visit versus 40 (6.4%) hospitalized and 14 (2.2%) with ER visits for infants in the PA-approved group (P = 0.055 and P = 0.019, respectively); 15 (4.3%) of the PA-denied group had either a hospitalization or an ER visit versus 42 (6.6%) in the PA-approved group (P = 0.060). One patient in the palivizumab PA-approved group died. Over the 3 RSV seasons, the mean number of palivizumab doses and mean allowed palivizumab cost per treatment episode (per infant per season) were 3.64 and $6,950, respectively, and the average allowed palivizumab cost was $7,702 per utilizing infant. Total per infant costs for palivizumab, RSV hospitalizations, and RSV-related ER visits were $8,534 for infants receiving palivizumab compared with $223 for those denied palivizumab coverage (P = 0.002). Drug cost avoidance associated with the PA program was estimated to be $2,418,600 (348 infants times $6,950 palivizumab cost per episode) over the 3 RSV seasons. In a 500,000-member health plan, a PA program to restrict palivizumab use in accordance with AAP recommendations was associated with estimated palivizumab drug cost avoidance of more than $2.4 million over 3 years. There was no significant difference in the RSV-related hospitalization rate for the PA-denied versus the PA-approved groups, but the PA-denied group had a slightly lower rate of RSV-related ER visits.

The 2009 COID Recommendations for RSV Prophylaxis: Issues of Efficacy, Cost, and Evidence-Based Medicine

The American Academy of Pediatrics (AAP) Committee on Infectious Disease (COID) recently published its updated recommendations for palivizumab prophylaxis for infants at high risk for severe respiratory syncytial virus (RSV) infection.1 Comparison of these guidelines with those published in 20062 reveals changes that would significantly decrease the number of premature infants who would be considered for palivizumab prophylaxis. The most notable changes in the 2009 guidelines are the indications for prophylaxis in premature infants 32 to 35 weeks' gestational age (GA). These changes included: 1. decreasing the chronological age (CA) for infants 32 to 35 weeks' GA for whom palivizumab would be considered from 6 months to 90 days of age at the start of RSV season (in addition, these infants should have at least 1 more risk factor [ie, day care attendance and/or have sibling(s) <5 years of age]); and 2. continuing palivizumab in these infants only until they reach a CA of ≥90 days (ie, a total of 1–3 doses based on date of birth). We believe that some aspects of the new guidelines extend beyond the available evidence-based data and merit discussion. ![Graphic][1] For further study of the AAP's policy on RSV treatments, download “RSV: Prevention of Disease”. This complementary issue of PREP® Audio is being offered exclusively to Pediatrics subscribers and AAP members. This is a must hear for all pediatricians! Current evidence indicates that young CA (infants born within 3 months before or during the RSV season) is an independent risk factor for RSV hospitalization during that RSV season.3 Law et al4 also documented that infants 33 to 35 weeks' GA born between November and January were at increased risk for RSV hospitalization throughout that season. Although they noted higher RSV-related hospitalization rates in 33- to 36-week-GA infants at a CA of … Address correspondence to Leonard R. Krilov, MD, Winthrop University Hospital, 120 Mineola Blvd, Suite 210, Mineola, NY 11501. E-mail: lkrilov{at}winthrop.org [1]: /embed/inline-graphic-1.gif

Incidence of respiratory syncytial virus-related hospitalizations in high-risk children: follow-up of a national cohort of infants treated with Palivizumab as RSV prophylaxis.

The prophylactic administration of Palivizumab, a monoclonal antibody binding the respiratory syncytial virus (RSV) fusion protein, was recently shown to significantly decrease the incidence of RSV-related hospitalizations among high-risk children (IMpact-RSV trial). While awaiting marketing authorization in France and through a cohort of patients' name-based national program temporarily authorized by the French Drug Agency, a prospective register of all Palivizumab-treated patients in France was set up during the epidemic season 1999-2000. Based on this register, this study was carried out to evaluate the incidence of RSV-related hospitalizations and the safety of prophylaxis among a national cohort of children at high-risk of severe RSV disease. During the study period, guidelines issued by the French Pediatric Society recommended prophylaxis for children either aged less than 6 months at inclusion and born at less than 33 weeks of gestation with a history of bronchopulmonary dysplasia (BPD) at 28 days of life, or aged less than 2 years, born at less than 36 weeks of gestation, and having required treatment for BPD over the previous 6 months. Once included in the program, investigators were to prospectively report the clinical and demographic characteristics of children, all hospitalizations, and reasons for the hospitalizations. Five hundred and sixteen children were treated with 1-5 monthly doses. The median gestational age was 28 weeks, and children born at less than 33 weeks of gestation accounted for 88% of the cohort. The prevalence of BPD was 81%. Ninety children were hospitalized for respiratory illness. In 39 children, hospitalizations were attributed to RSV (7.6% of the total cohort). Among those 39 children, 10 (1.9% of the total cohort) required admission into an intensive care unit, and 4 required mechanical ventilation. No deaths or serious adverse events attributable to RSV infection or Palivizumab treatment were reported. We conclude that the RSV-related hospitalization rate in this high-risk cohort was comparable to the rate observed in the subgroup of Palivizumab-prophylaxed children with BPD in the IMpact-RSV trial.