RSV-related Hospitalization Research Articles

Efficacy and long-term outcomes of palivizumab prophylaxis to prevent respiratory syncytial virus infection in infants with cystic fibrosis in Northern Ireland.

RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002. To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post-introduction of palivizumab prophylaxis. A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed. Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P < 0.025) with a relative risk of 2.5. Chronic PA infection at 6 years remained low in both groups, with similar lung function and growth parameters. Total costs were calculated at £96,127 ($151,880) for the non-recipient cohort versus £137,954 ($217,967) for the recipient cohort. Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests.

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.

Anti-RSV prophylaxis efficacy for infants and young children with cystic fibrosis in Ireland.

RationaleThere is limited evidence supporting the routine use of palivizumab in paediatric cystic fibrosis (CF) patients to reduce respiratory syncytial virus (RSV) infection and related hospitalisation. Despite this, anti-RSV prophylaxis is increasingly common. This is the first report from Ireland regarding palivizumab outcomes for children with CF, under 2 years old, despite the greatest prevalence of CF globally.MethodsAn audit was performed at a tertiary hospital in Ireland’s mid-West to document all children with CF, <24 months old, who received palivizumab over a five year period and comparision made with all eligible children for the prior five year period who had not received the product (also CF patients). Palivizumab was administered to both cohorts in their first year of life. Hospitalisation rates were compared using Fisher’s exact test. Incidence of RSV and Pseudomonas aeruginosa infection was recorded.ResultsA total of 19 patients who received palivizumab were included in the study; comparision was made with a retrospective control group of 30 patients. Prophylactic palivizumab did not prevent hospitalisation for 10/19 patients, 3 of whom were affected by RSV. This was significantly greater than in the control group, where no hospitalisations were recorded (p < 0.0001). P. aeruginosa was isolated in one case from the study cohort, while no P. aeruginosa was detected in the control group.ConclusionsThis study, the first of its kind from Ireland where CF prevalence is highest, does not provide unequivocal support for prophylactic use of palivizumab in CF patients under 2 years. Despite being derived from a small sample size, based on these data and complementary clinical observation, we have discontinued such prophylaxis. However, should reported incidence of RSV-related hospitalisation increase, there is scientific plausibility for appropriately powered, randomised, controlled trials of palivizumab.

Anti-RSV prophylaxis efficacy for infants and young children with cystic fibrosis in Ireland

Rationale: There is limited evidence supporting the routine use of palivizumab in paediatric cystic fibrosis (CF) patients to reduce respiratory syncytial virus (RSV) infection and related hospitalisation. Despite this, anti-RSV prophylaxis is increasingly common. This is the first report from Ireland regarding palivizumab outcomes for children with CF, under 2 years old, despite the greatest prevalence of CF globally.&#x0D; Methods: An audit was performed at a tertiary hospital in Ireland’s mid-West to document all children with CF, &lt;24 months old, who received palivizumab over a five year period and comparision made with all eligible children for the prior five year period who had not received the product (also CF patients). Palivizumab was administered to both cohorts in their first year of life. Hospitalisation rates were compared using Fisher’s exact test. Incidence of RSV and Pseudomonas aeruginosa infection was recorded.&#x0D; Results: A total of 19 patients who received palivizumab were included in the study; comparision was made with a retrospective control group of 30 patients. Prophylactic palivizumab did not prevent hospitalisation for 10/19 patients, 3 of whom were affected by RSV. This was significantly greater than in the control group, where no hospitalisations were recorded (p &lt; 0.0001). P. aeruginosa was isolated in one case from the study cohort, while no P. aeruginosa was detected in the control group.&#x0D; Conclusions: This study, the first of its kind from Ireland where CF prevalence is highest, does not provide unequivocal support for prophylactic use of palivizumab in CF patients under 2 years. Despite being derived from a small sample size, based on these data and complementary clinical observation, we have discontinued such prophylaxis. However, should reported incidence of RSV-related hospitalisation increase, there is scientific plausibility for appropriately powered, randomised, controlled trials of palivizumab.

12: Lean Management and Just-in-Time Ordering Reduces Palivizumab Wastage in a Provincial RSV Prophylaxis Program

Immunoprophylaxis with palivizumab is recommended for infants at high risk of RSV-related hospitalization. Palivizumab is an expensive sole-sourced biologic pharmaceutical available in single dose vials which expires 6 h upon reconstitution, resulting in potentially high rates of drug wastage. Palivizumab has a short shelf life and requires cold-chain storage making left-over inventory costly and undesirable. Principles of Lean production and Just-In-Time production can be applied to minimize wastage and costs. To describe the outcome of Lean management and Just-In-Time inventory control in the operations of a provincial RSV immunoprophylaxis program. The Manitoba RSV Immunoprophylaxis Program (MB RSVP) coordinates the use of palivizumab for eligible patients in the province of Manitoba, Canada, a region of 650,000 square km with population of 1.27 million. Yearly PDCA cycles using Lean management principles have resulted in a centralized provincial coordinating centre that manages RSV immunoprophylaxis including patient enrolment, coordination of injection through a network of health care providers (to allow for cohorting and vial sharing), just-in-time ordering and shipping of palivizumab to clinic sites, and continuious inventory tracking. Dosing reports from sites function as a Kanban system triggering future shipment of palivizumab. Regular discussion with all involved in the Program fosters involvement, problem solving, and continuous improvement. The overall objective is limitation of wastage while maximizing patient benefit. Over three seasons (2011–2014), the MB RSVP enrolled and organized RSV immunoprophylaxis for 868 patients with over 3500 doses provided. The Program was effective in limiting wastage of palivizumab (mg of drug ordered but not given to patient) to 10% (range 8.4% to 12.8% per year). Just-in-time ordering reduced left over inventory from 157 vials (in 2012) to 75 vials (in 2014) resulting in a decreased inventory carrying cost from $118,000 to $56,000 Canadian respectively ($752/50 mg). Using Lean business management principles and Just-In-Time inventory control resulted in minimum wastage of palivizumab and decreased yearly left-over inventory of palivizumab in a provincial RSV prophylaxis program.

121: High Adherence with RSV Immunoprophylaxis Dosing Schedule in a Centrally Managed Provincial RSV Program

Passive immunization against RSV requires monthly doses to maintain adequate serologic levels to prevent RSV-related hospitalization. Up to five IM doses may be provided during the RSV season. Although patients enrolled into a RSV prophylaxis program are already pre-selected because of underlying risk factors, and self-selected by parental agreement to immunoprophylaxis, ensuring adherence to the monthly dosing schedule and the total number of doses remains a challenge. To review the adherence to dosing schedule and number of doses for patients enrolled in a provincial RSV Prophylaxis Program. The Manitoba RSV Prophylaxis Program (MB RSVP) coordinates RSV immunoprophylaxis for all patients in the province of Manitoba. This centralized program manages all aspects of RSV immunoprophylaxis including patient enrolment and medication ordering. One benefit of this centralized program is tracking of doses received and subsequent dose schedule for all enrolled patients. The MB RSVP provides phone calls reminding patients and health care providers (HCP) of upcoming palivizumab doses. Anonymized data for three seasons (2011–14) were analyzed. Adherence was evaluated by number of doses received during the season and by adherence to the dosing schedule. The optimum number of doses a patient should receive was calculated from the date of first dose given to the end of the RSV prophylaxis season. Compliance with dosing schedule is calculated based on the provincial standardized dosing interval of 28 days with exception of 35 days between the fourth and fifth doses. Over the three seasons, 857 paediatric patients received at least one dose of palivizumab. 74.8% of patients received the expected number of doses during the season and 24% received less than expected. Overall, 58.4% of all doses were provided exactly according to schedule. (either exactly at 28 days interval, or exactly at 35 days interval between 4th and 5th doses). 81.1% of doses were given within a ± 3 day window around the scheduled date, 93% within ± 7 day window. Only 13.5% of all doses were given ≥4 days after schedule. Factors impacting adherence included parent or HCP non-compliance, patient death, loss-to-follow-up, relocation outside of province, vacation/travel, repair of cardiac lesion, and withdrawal of consent. A centralized provincial RSV prophylaxis program with central tracking of dosing schedule and regular phone reminder to parents and heath care providers is highly successful in ensuring adherence to both dosing schedule and total number of doses.

Value of a risk scoring tool to predict respiratory syncytial virus disease severity and need for hospitalization in term infants.

Several environmental and demographic risk factors have been validated and are used to determine the risk of acquiring severe respiratory syncytial virus (RSV) infection and subsequent hospitalization in late preterm infants born at 33-35 weeks gestational age. The applicability of the same composite model of risk factors in the term population has not been fully explored. The primary objective of this pilot study was to establish whether a risk scoring tool (RST), could predict the severity of RSV infection in term, RSV-positive infants who were hospitalized. A retrospective observational study was conducted in a pediatric unit, over 2 RSV seasons (2011-2013). A convenient sample of 72 children was selected out of a total of 111 RSV-positive cases after exclusions. The RST was applied and a score of respiratory disease severity was determined for each patient. Demographic characteristics were analyzed by standard descriptive methods, χ(2) analysis was utilized for categorical data and ANOVA for comparison between the clinical severity groups and the RST score. A P-value <0.05 was considered significant. Sixty per cent (n = 43) of all infants scored in the low-risk category compared to 26% (n = 19) in the moderate and 14% (n = 10) in the high-risk groups. RST scores were also inconsistent with disease severity. Mean (SD) RST scores for those with mild, moderate, and severe illness were 47.8 [16.4], 41.1 [20.39] and, 41.7 [19.8], respectively (P = 0.17). In conclusion, the RST did not predict accurately the clinical severity of RSV bronchiolitis in term infants nor did it correlate with risk for RSV-related hospitalization.

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.

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.

Serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in high-risk infants

Monthly doses of palivizumab, an RSV-specific monoclonal antibody, reduce RSV-related hospitalizations (RSVH) in high-risk children; however, no specific palivizumab level has been correlated with disease severity in humans. A post hoc analysis of a previous randomized, placebo-controlled trial evaluated the relationship between serum palivizumab level at the time of RSVH and disease severity. Pediatric intensive care unit (PICU) admission was the primary severity marker. Relationships were evaluated between disease severity and gestational age, age at enrollment, age at RSVH, presence of bronchopulmonary dysplasia, sex, race, multiple birth, household smoking, daycare attendance, sibling(s), family history of atopy, duration between most recent palivizumab dose and RSVH, and palivizumab level at RSVH. Forty-two (87.5%) of 48 palivizumab recipients with RSVH had palivizumab levels drawn; 11 were admitted to the PICU. Mean palivizumab levels were lower in PICU-admitted subjects (47.2 μg/mL) vs. non-PICU subjects (98.7 μg/mL; P < 0.0001); there were no statistically significant differences in other variables examined. The probability of PICU admission declined with higher palivizumab levels; there were no PICU admissions with levels ≥ 92 μg/mL. In multivariate analyses, palivizumab level was the only independent predictor of PICU admission (P = 0.009). Palivizumab level also correlated with duration of RSVH and PICU stay, supplemental oxygen use and duration, and mechanical ventilation use and duration (P < 0.05). Higher palivizumab level was associated with decreased disease severity in high-risk infants with RSVH. Findings suggest that palivizumab level has clinical relevance, and adherence to timely monthly dosing may confer additional protection among high-risk children receiving palivizumab.

An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization

Post-infectious immunity to respiratory syncytial virus (RSV) infection results in limited protection as evidenced by the high rate of infant hospitalization in the face of high titer, maternally derived RSV-specific antibodies. By contrast, RSV fusion (F) glycoprotein antigenic site II humanized monoclonal antibodies, palivizumab and motavizumab, have been shown to reduce RSV-related hospitalization in infants. Immunogenicity and efficacy studies were conducted in cotton rats comparing a recombinant RSV F nanoparticle vaccine with palivizumab and controlled with live RSV virus intranasal immunization and, formalin inactivated RSV vaccine. Active immunization with RSV F nanoparticle vaccine containing an alum adjuvant induced serum levels of palivizumab competing antibody (PCA) greater than passive administration of 15mg/kg palivizumab (human prophylactic dose) in cotton rats and neutralized RSV-A and RSV-B viruses. Immunization prevented detectable RSV replication in the lungs and, unlike passive administration of palivizumab, in the nasal passage of challenged cotton rats. Histology of lung tissues following RSV challenge showed no enhanced disease in the vaccinated groups in contrast to formalin inactivated ‘Lot 100’ vaccine. Passive intramuscular administration of RSV F vaccine-induced immune sera one day prior to challenge of cotton rats reduced viral titers by 2 or more log10 virus per gram of lung and nasal tissue and at doses less than palivizumab. A recombinant RSV F nanoparticle vaccine protected lower and upper respiratory tract against both RSV A and B strain infection and induced polyclonal palivizumab competing antibodies similar to but potentially more broadly protective against RSV than palivizumab.

The Effect of Birth Month on the Risk of Respiratory Syncytial Virus Hospitalization in the First Year of Life in the United States

Respiratory syncytial virus (RSV) is the most common cause of severe respiratory illness in infants. To help direct targeted interventions and future RSV vaccine programs, we examined risk of RSV-related hospitalization by infant age and birth month. We conducted Poisson regression analyses to evaluate birth month as a risk factor for RSV-related pediatric hospitalizations (identified by any mention of ICD-9-CM diagnosis codes: 466.11, 480.1 or 079.6) from State Inpatient Data in Arizona, Iowa, New York, Oregon and Wisconsin between July 1996 and June 2006. We used an age cohort approach to compute total relative risk of RSV during the first year of life. We identified 82,296 RSV-related infant hospital admissions, corresponding to 13.9 per 1000 person-years among infants <12 months of age. Of these, 42% of the patients were female and 73% were <6 months old. One-month-old infants born in January were ~10 times more at risk for RSV-related hospitalization than 1-month-old infants born in October [relative risk: 9.8 (7.8-12.4)]. Across the first year of life, infants born in December and January had a 2- and 3-fold higher risk, respectively, of an RSV-related hospitalization event than infants born in July. Birth month and age at admission impacted the risk of RSV-related hospitalization within the first year of life in 5 states we investigated. As RSV vaccine candidates are currently under investigation in clinical trials, our findings help identify ideal RSV vaccine schedules to prevent early and severe events while improving the use of expensive prophylactic drugs.

Respiratory Syncytial Virus Prophylaxis in Down Syndrome: A Prospective Cohort Study

Background/Objective: Down syndrome (DS) children are at significant risk for respiratory tract (RTI) and respiratory syncytial virus (RSV) infection and hospitalization. We compared hospitalization rates for RTI in DS children aged < 2 years given palivizumab in the RSV season versus a previously published, similar untreated DS birth cohort. Methods: 532 prophylaxed DS children were from the Canadian palivizumab registry (CARESS) between 2005-2012. The untreated group comprised 233 DS children derived from a Dutch, nation-wide birth cohort from 2003-2005. Events during the RSV seasons were counted. Demographics and risk factors were compared using t-test or chi-square where appropriate. Poisson regression analysis was performed to compare incidence rate ratios [95% CI] for both RTI and confirmed RSV hospitalization between the groups while controlling for observation length and known risk factors for severe RSV infection. Results: In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects compa red to palivizumab recipients (incidence rate ratio 3.63 [95% CI: 1.52-8.67], p=0.004). The adjusted risk for hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11 [0.80 – 1.55], p=0.53). Conclusions: These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in DS children aged <2 years. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high risk patient population.

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

Clinical Characteristics and Direct Medical Cost of Respiratory Syncytial Virus Infection in Children Hospitalized in Suzhou, China

There have been few studies on children hospitalized with respiratory syncytial virus (RSV) published from mainland China. We performed a retrospective review of medical charts to describe the epidemiology, clinical features and direct medical cost of laboratory-proven RSV children hospitalized in Suzhou, China. Testing is routine for RSV for children admitted to the respiratory ward at Suzhou University Children's Hospital. We performed a retrospective study on children with documented RSV infection hospitalized at Suzhou University Children Hospital during 2005-2009 using a structured chart review instrument. A total of 2721 hospitalized children (15.0% of those tested) were positive by immunofluorescent assay for RSV during 2005-2009, and 64.0% of them were male. Eighty-seven percentage of the RSV-infected children were 2 years old and younger, and 56.6% were ≤ 6 months of age. The median length of hospital stay was 8 days. Of the RSV-infected children, 92.5% developed pneumonia and 21.8% experienced wheezing. In total, 49 (5.1%) of RSV-positive children were transferred to the ICU. Children ≤ 6 months old and who had congenital heart disease had higher risk of severe RSV disease. The mean cost of each RSV-related hospitalization was US$571.8 (US$909.6 for children referred to ICU and US$565.4 for those cared for on the wards). Multivariable logistic regression showed that compared with the ≤ 6 months children, those aged >6 months old had higher hospitalization cost; children with respiratory distress or with chronic lung diseases tended to have higher hospitalization costs than others. RSV infections and severe RSV diseases mostly occurred in early infancy. The direct medical cost was high relative to family income. Effective strategies of RSV immunization of young children in China may be beneficial in addressing this disease burden.

Comparison of the timing of initial prophylactic palivizumab dosing on hospitalization of neonates for respiratory syncytial virus

The effects of two prophylactic palivizumab schedules on hospitalization of neonates for respiratory syncytial virus (RSV) were compared. This retrospective study was conducted in the neonatal intensive care unit (NICU) of a tertiary care, academic medical center. Patients were divided into two groups. Group 1 (hospitalized between October 2005 and April 2007) received inpatient doses of palivizumab monthly throughout the RSV season, regardless of their anticipated discharge date, followed by outpatient doses. Group 2 (hospitalized between October 2007 and April 2009) received only one dose of palivizumab before hospital discharge with subsequent outpatient doses. The primary outcome measure was the number of hospitalizations for RSV bronchiolitis. Secondary endpoints included the total number of palivizumab doses each patient received, number of inpatient doses per patient, number of hospitalizations requiring intensive care unit admission, patient need for mechanical ventilation, outcome of the RSV-related hospitalization, and cost of inpatient palivizumab doses per patient. A total of 207 neonates were included in the study (112 in group 1, 95 in group 2). The mean gestational age was 29.7 weeks in group 1 and 30.3 weeks in group 2. Seven patients were hospitalized for RSV infection (5 in group 1 versus 2 in group 2, p = 0.4564). No RSV-related deaths occurred. Significantly more inpatient doses were administered to group 1 versus group 2 (1.7 versus 1, p < 0.001). Limiting inpatient palivizumab to 1 dose before discharge resulted in an institutional cost savings of more than $60,000 annually. Hospitalization rates for RSV did not significantly differ between NICU patients who received inpatient prophylactic palivizumab monthly and those who received only one dose before discharge.

Association of RSV-related hospitalization and non-compliance with palivizumab among commercially insured infants: a retrospective claims analysis.

BackgroundPalivizumab has been shown to decrease the incidence of hospitalization due to respiratory syncytial virus (RSV) in infants at risk of severe RSV disease. We examined the association between compliance with palivizumab dosing throughout the RSV season and risk of RSV-related hospitalization in clinical practice.MethodsSubjects who were born and discharged from the hospital before the RSV season and received ≥1 palivizumab dose during their first RSV season were identified from a large US commercial health insurance database between 01/01/03 and 12/31/09. Subjects were deemed compliant if they received ≥5 palivizumab doses without gaps (>35 days) and their first dose was received by November 30. RSV-related hospitalizations were identified using ICD-9-CM diagnosis codes and examined over 2 observation periods: post-index dose and RSV season. A Cox proportional hazard model was used to evaluate the association between non-compliance and RSV-related hospitalization.ResultsOf the 5,003 subjects who received palivizumab, 62% were deemed non-compliant. Non-compliant subjects had significantly higher unadjusted rates of RSV-related hospitalizations compared to compliant subjects during both observation periods (post-index: 6.1 vs. 2.8 per 100 infant seasons, p < 0.001; RSV season: 5.9% vs. 2.3%; p < 0.001). In multivariate analyses, non-compliance was significantly associated with higher risk of RSV-related hospitalization (HR = 2.01; p < 0.001). Of the 225 RSV-related hospitalizations observed during the RSV season, 61 (27%) occurred before the first dose of palivizumab.ConclusionsSubjects who did not receive monthly dosing of palivizumab throughout the RSV season had significantly higher rates of RSV-related hospitalizations. The RSV-related hospitalizations prior to the first dose of palivizumab suggest some dosing was started too late.

Validity of Laboratory-based Surveillance for Detection of Respiratory Syncytial Virus Seasons

In this study, we validated the Centers for Disease Control and Prevention's use of a 10% threshold of median proportion of positive laboratory tests (median proportion positive (MPP)) to identify respiratory syncytial virus (RSV) seasons against a standard based on hospitalization claims. Medicaid fee-for-service recipients under 2 years of age from California, Florida, Illinois, and Texas (1999-2004), continuously eligible since birth, were categorized for each week as high-risk or low-risk with regard to RSV-related hospitalization based on medical and pharmacy claims data and birth certificates. Weeks were categorized as on-season if the RSV hospitalization incidence rate in high-risk children exceeded the seasonal peak of the incidence rate in low-risk children. Receiver operating characteristic (ROC) curves were used to measure the ability of MPP to discriminate between on-season and off-season weeks as determined from hospitalization data. Areas under the ROC curve ranged from 0.88 (95% confidence interval: 0.83, 0.92) in Illinois to 0.96 (95% confidence interval: 0.94, 0.98) in California. Requiring at least 5 positive tests in addition to the 10% MPP threshold optimized accuracy, as indicated by minimized root mean square errors. The 10% MPP with the added requirement of at least 5 positive tests is a valid method for identifying clinically significant RSV seasons across geographically diverse states.

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.