Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis

OBJECTIVES: To assess the risk of hospitalization associated with respiratory syncytial virus (RSV) and to estimate the economic impact of RSV prophylaxis with either RSV immune globulin (RSV-Ig) or RSV monoclonal antibody (palivizumab) on a cohort of preterm infants born at 32 weeks' gestation or earlier. DESIGN: Historical cohort study. SETTING: A 12-county neonatal network served by the regional center in Rochester, NY. PARTICIPANTS: One thousand twenty-nine infants born at 32 weeks' gestation or earlier followed up until 1 year of corrected age. MAIN OUTCOME MEASURES: Rate of hospitalization with an RSV-associated illness; cost per hospitalization prevented resulting from either form of RSV prophylaxis. RESULTS: The probability of hospitalization with an RSV-associated illness for infants born at 32 weeks' gestation or earlier was estimated at 11.2%. The incidence of RSV hospitalization increased with decreasing gestational age (13.9% vs 4.4% for infants born at < or =26 weeks' gestation vs those born at 30-32 weeks' gestation). Infants requiring respiratory support at 36 weeks of postconceptual age (PCA) or older had a higher hospitalization rate (16.8% vs 6.2%), longer hospital stays, and higher hospital charges than infants requiring respiratory support at less than 36 weeks of PCA. For infants requiring respiratory support at less than 36 weeks of PCA, the incidence of RSV hospitalization still increased with decreasing gestational age (10.2% vs 4.3% for infants < or =26 weeks' gestation vs those 30-32 weeks' gestation). Analysis indicated that both forms of RSV prophylaxis would increase the net cost of care for all groups. Palivizumab was more cost-effective than RSV-Ig for preventing RSV hospitalization among infants who required respiratory support at less than 36 weeks of PCA, especially those born at 26 weeks' gestation or earlier. Overall, RSV-Ig was more cost-effective than palivizumab for infants requiring respiratory support at 36 weeks of PCA or older. CONCLUSIONS: This analysis suggests that available forms of RSV prophylaxis would increase the net cost of care not only for the entire cohort but for each of the subgroups studied. However, the RSV hospitalization rate and the cost-effectiveness of prophylaxis varied markedly by subgroup.     

Net cost of palivizumab for respiratory syncytial virus prophylaxis during the 1998/99 season in northern Alberta

OBJECTIVE:

Palivizumab has been shown to decrease respiratory syncytial virus (RSV) hospitalization rates in preterm infants and infants with chronic lung disease. The objective of the present study was to determine whether the use of palivizumab during the 1998/99 RSV season would have resulted in a cost-saving in infants discharged from Edmonton hospitals.

DESIGN:

A retrospective study of RSV hospitalizations was performed by contacting parents and reviewing hospital lists. The net cost of using palivizumab was determined by comparing the cost of giving the drug from November 1, 1998 to April 1, 1999 with the cost of potentially averted medical transports and hospitalizations.

POPULATION:

One hundred fifty-nine infants discharged from Edmonton hospitals who met the Canadian Paediatric Society’s criteria for receiving palivizumab during the 1998/99 RSV season were studied.

RESULTS:

The cost of using palivizumab in these 159 study infants would have been $753,300. The infants had 21 RSV hospitalizations and required four medical transports. The estimated cost of RSV hospital-based care for these infants was $168,888. Assuming a drug efficacy of 39% in infants with chronic lung disease and 78% in infants born before 33 weeks’ gestation with no chronic lung disease, $121,147 of these costs could have been averted if palivizumab had been used.

CONCLUSIONS:

The net cost to the health care system of using palivizumab, as recommended in the Canadian Paediatric Society guidelines, in study infants in northern Alberta during the 1998/99 RSV season would have been $632,153.     

Palivizumab prophylaxis of respiratory syncytial virus infection in high-risk infants

Palivizumab prophylaxis significantly reduces hospitalization for respiratory syncytial virus (RSV) disease in preterm infants. However, palivizumab is very expensive. Data from a New Zealand cost-effectiveness analysis were considered by representatives of the Infectious Diseases and Immunisation, Fetus and Newborn, and Respiratory Committees of the Paediatric Society of New Zealand. Prophylaxis in all high-risk groups was associated with net cost. The consensus panel recommends that the priority for palivizumab be given to babies discharged on home oxygen with chronic lung disease, followed by babies born at 28 weeks or less gestation.     

Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany

Palivizumab (Synagis, MedImmune Inc./Abbott Laboratories) has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in premature infants. The cost-effectiveness ratio of this prophylaxis, however, has not been evaluated in the German health-care system to date. The aim of the study was to assess the costs and benefits of Palivizumab among premature infants 相似文献   

Prophylaxis for respiratory syncytial virus with respiratory syncytial virus-immunoglobulin intravenous among preterm infants of thirty-two weeks gestation and less: reduction in incidence, severity of illness and cost

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) prophylaxis among preterm infants of < or =32 weeks gestation by comparing the severity of illness and cost of RSV-related care during the two winter seasons before (1994 to 1995, 1995 to 1996) with the two seasons after initiation of prophylaxis (1996 to 1997, 1997 to 1998). METHODS: Preterm infants of < or =32 weeks gestation at risk for hospitalization with RSV infection were identified retrospectively from the infants hospitalized in our neonatal units. Infants were included if they (1) were born 6 months before or during four winter seasons (1994 to 1998), (2) were discharged from the neonatal unit and (3) had remained in the university outpatient clinic system during at least the first winter of life. Preterm infants of < or =32 weeks gestation hospitalized with RSV were identified from our RSV database (which includes cost of hospitalization, duration of hospital stay, pediatric intensive care unit stay and intubation). Infants receiving prophylaxis were identified prospectively. RESULTS: The incidence of hospitalization with RSV was significantly lower among the cohort of infants born after initiation of prophylaxis: 8.7% (17 of 195) vs. 22% (35 of 159), P = 0.00049 by two tailed Fisher's exact test. Among the cohort of infants born after initiation of prophylaxis (n = 195), 100 infants received prophylaxis. The gestational and chronologic ages of the prophylaxis-treated infants were significantly lower than those of the non-prophylaxis-treated infants (n = 95). The prophylaxis-treated infants also were more likely to have bronchopulmonary dysplasia. Only 1 (1%) of the prophylaxis-treated infants required hospitalization for RSV. Comparison of the cohort of infants born before initiation of prophylaxis to the cohort born after initiation of prophylaxis (includes prophylaxis-treated and non-prophylaxis-treated infants) revealed a significant reduction in severity of illness and cost. The length of stay in the cohort born before initiation of prophylaxis was reduced 83.8%: 373.6 days per 100 infants at risk vs. 60.5 (P = 0.00055). The length of stay in the pediatric intensive care unit was reduced 92.7%: 218.2 days per 100 infants at risk vs. 15.9 (P = 0.00029). The duration of intubation was reduced 95.6%: 187.4 days per 100 infants at risk vs. 8.2 (P = 0.00024). The dollars spent for RSV-related care (hospitalizations and prophylaxis) per 100 infants at risk for RSV was reduced 65% in the cohort of infants born after prophylaxis: $670,590 per 100 infants at risk vs. $234,596 (P = 0.00056). This reduction remained significant (64.9%) if the cost of ribavirin (drug and administration fees) was excluded from the cost of hospitalization. CONCLUSIONS: These data reveal that RSV prophylaxis significantly reduced the incidence of RSV hospitalizations and severity of illness as well as the cost of RSV-related care among these infants.     

Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden

Aim: To investigate the cost‐effectiveness of palivizumab vs. no prophylaxis for respiratory syncytial virus (RSV) infection in preterm infants in Sweden. Methods: A probabilistic Markov model was populated using a nationwide register linkage and data from the literature. Cost‐effectiveness was investigated from a societal perspective over a lifetime for infants born at <29 weeks of gestation. Palivizumab was modelled using assumptions for its direct effect on RSV hospitalization risk and an indirect effect (via decreased RSV hospitalization) on subsequent asthma and mortality during the epidemic. Costs and effects were discounted by 3%. Results: In the base case, prophylaxis resulted in an additional 0.102 quality‐adjusted life‐year (QALY) at a cost of 20 000 SEK relative to no prophylaxis (incremental cost‐effectiveness ratio [ICER] 195 000 SEK/QALY). The probability of prophylaxis being cost–effective was 99% at a willingness‐to‐pay of 500 000 SEK/QALY. Assumptions about a causal association between RSV infection and subsequent asthma had a moderate impact, while exclusion of the indirect prophylaxis effect on mortality increased the ICER to 492 000 SEK/QALY. When excluding both of these, prophylaxis was not cost–effective. Conclusion: Based on a willingness‐to‐pay of 500 000 SEK/QALY, palivizumab was found to be cost–effective compared with no prophylaxis for infants born at <29 weeks if severe RSV infection was assumed to increase subsequent asthma or mortality risk.     

Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalization in preterm infants and infants with chronic lung disease (CLD). Palivizumab, a humanized monoclonal antibody, was approved in Europe in 1999 as prophylaxis against severe RSV-related respiratory illness. No multiple season data have been published on palivizumab effectiveness in European populations. Data collected during 4 years in Spain compared RSV hospitalization rates and risk factors in a cohort of palivizumab-prophylaxed and nonprophylaxed preterm infants. METHODS: The first cohort was derived from 2 previous studies and included 1583 infants followed during 2 RSV seasons (1998 to 1999, 1999 to 2000) before palivizumab initiation in Spain. The second cohort included 1919 infants who received palivizumab prophylaxis for 2 subsequent respiratory seasons (2000 to 2001, 2001 to 2002). Both cohorts were preterm (< or =32 weeks gestational age) and < or =6 months old at onset of RSV season. RESULTS: The RSV hospitalization rate in the palivizumab-prophylaxed cohort was 3.95, and it was 13.25% in nonprophylaxed infants This 70% overall difference in RSV hospitalization was observed despite the palivizumab-prophylaxed group's lower gestational ages, more severe neonatal intensive care unit respiratory courses and higher incidence of CLD. Significant risk factors for RSV hospitalization in both cohorts included: lower gestational age; chronologic age <3 months at RSV season onset; school age siblings; and lower parental education. Nonprophylaxed children had a higher risk for RSV-related hospitalization than did prophylaxed patients (odds ratio, 3.86; 95% confidence interval, 2.83 to 5.25). CONCLUSION: Data from this study support the effectiveness of palivizumab in significantly modifying RSV-related hospitalizations in high risk preterm infants, with and without CLD, during two respiratory seasons.     

Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease

OBJECTIVES: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants without chronic lung disease and to evaluate the impact on cost-effectiveness of a potential reduction in risk of asthma following respiratory syncytial virus infection among infants receiving palivizumab. DESIGN: Two decision analytic models were designed, one with and the other without accounting for increased risk of asthma following respiratory syncytial virus infection. SETTING: A hypothetical community or university hospital. PARTICIPANTS: Hypothetical cohorts of infants without chronic lung disease born at 26 to 32 weeks' gestation. INTERVENTIONS: Palivizumab prophylaxis vs no prophylaxis. MAIN OUTCOME MEASURES: Expected costs and incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year. RESULTS: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratios were high for all gestations and are not considered cost-effective by today's standards (<$200 000 per quality-adjusted life-year). Both models were sensitive to variation in the cost of palivizumab. The model that included asthma was sensitive to variation in quality of life for children with asthma. In instances where asthma was considered severe with profound worsening in quality of life compared with life without asthma, some infants had an incremental cost per quality-adjusted life-year that was less than $200 000. CONCLUSIONS: Our model supports implementing more restrictive guidelines for palivizumab prophylaxis. Palivizumab was cost-effective for some infants in an analysis that accounted for increased risk of severe asthma following respiratory syncytial virus infection.     

Impact of palivizumab prophylaxis on respiratory syncytial virus hospitalizations in high risk Alaska Native infants

BACKGROUND: Alaska Native children experience extremely high rates of hospitalization for respiratory syncytial virus (RSV) infection. We evaluated the effect of palivizumab prophylaxis on the incidence of RSV hospitalizations in high risk Alaska Native children. METHODS: We analyzed two retrospective cohorts. The first analysis, of southwest Alaska Native children hospitalized with acute respiratory infections during 1993 to 1996 and 1998 to 2001, compared RSV hospitalization rates among premature and nonpremature infants born before (1993 to 1996) and after (1998 to 2001) palivizumab use. The second analysis, of Alaska Native infants with a history of prematurity or lung disease during 1998 through 2001, compared RSV hospitalization among children receiving palivizumab during protected periods (within 32 days after a dose of palivizumab) and unprotected periods. RESULTS: First RSV hospitalizations in premature infants from southwest Alaska meeting criteria for palivizumab prophylaxis decreased from 439 per 1000 births before to 150 per 1000 births after palivizumab (relative rate, 0.34; 95% confidence interval, 0.17 to 0.68), whereas the rate in nonpremature infants remained stable (148 per 1000 births compared with 142 per 1000). Among high risk Alaska Native children during 1998 through 2001, the rate of first RSV hospitalization was 0.55 per 1000 protected days and 1.07 per 1000 unprotected days (relative rate, 0.52; 95% confidence interval, 0.28 to 0.93). CONCLUSIONS: Palivizumab reduced RSV hospitalizations in high risk infants in a region with high rates of RSV hospitalization.     

Prevention of respiratory syncytial virus infections in high-risk infantsby monoclonal antibody (palivizumab)

Respiratory syncytial virus (RSV) is a major viral pathogen which causes serious respiratory illness in infants and children worldwide. Palivizumab (Synagis) is an anti-RSV monoclonal antibody administered intramuscularly for the prevention of severe RSV respiratory disease in high-risk infants and young children. The IMpact-RSV trial, the pivotal multicenter, randomized, placebo-controlled trial performed in the USA, Canada and the United Kingdom demonstrated an overall 55% reduction in hospitalization rate due to RSV infection in preterm infants (< or = 35 weeks gestation) with and without chronic lung disease (CLD). Subgroup analysis in premature infants without CLD revealed an even greater reduction in RSV hospitalization rates (78%). Adverse events were infrequent and did not differ between placebo and palivizumab groups. Injection site reactions were infrequent and mild; no differences were observed between palivizumab and placebo subjects. Palivizumab does not interfere with administration of other pediatric vaccines. Comprehensive parent education programs regarding prevention of infection, avoidance of risk factors for infection, careful adherence to infection control policies, and recognition of early symptoms of RSV infection remain important components of RSV prevention strategies. In light of the lack of effective vaccines for this serious health risk, palivizumab offers the only option for prophylaxis against RSV disease in high-risk infants.     

Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization and outcomes

OBJECTIVE: To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus (RSV) infection. DESIGN: Observational, prospective, longitudinal, multicenter study. SETTING: Eighteen hospitals and pediatric clinics located in six provinces across Canada. PATIENTS: Infants enrolled in the palivizumab Special Access Programme of Canada's Therapeutic Products Programme throughout the 1999 to 2000 RSV season. Most were premature infants born at < or = 32 weeks of gestation and/or had bronchopulmonary dysplasia. METHODS AND MAIN OUTCOME MEASURES: Neonatal and demographic data were recorded for each subject. The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections. RESULTS: There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000. Most subjects received 5 injections with high compliance. Prophylaxis was discontinued in 2% of children. There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children. Eighty-six of these were managed in an outpatient setting, and 30 required hospitalization. The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was 2.4%. Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%). CONCLUSIONS: This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings confirm the results of the major randomized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis.     

Prophylaxis of respiratory syncytial virus in Canada in 2003

Passive immunization of high-risk children with the humanized monoclonal antibody palivizumab is the mainstay of respiratory syncytial virus (RSV) prophylaxis in Canada in 2003. This product appears to be safe, and it prevents the majority of RSV hospitalizations in infants born before 36 weeks gestational age, and about half in children under 24 months of age with hemodynamically significant congenital heart disease. However, the high cost of palivizumab and the fact that at least 12 infants need to be treated throughout RSV season to prevent one hospitalization make it difficult to determine the ideal indications for the product. Because these high-risk infants account for a minority of RSV hospitalizations, it is desirable to search for a prophylactic strategy that is practical to apply in all infants.     

Risk Factors for Hospitalization due to Lower Respiratory Tract Infection in Preterm Infants on Palivizumab Prophylaxis

Objective

To determine the risk factors associated with lower respiratory tract infections (LRTI) related hospitalizations in preterm infants receiving palivizumab throughout the high season for respiratory syncytial virus (RSV) infection.

Methods

Premature infants who were commenced on palivizumab prophylaxis during the RSV season were included in the study following parental consent. Information on demographic, social, prenatal and postnatal clinical characteristics was recorded and risk factors associated with hospitalization were evaluated for each patient.

Findings

While 234 participants (Group 1, 92.8%) did not require hospitalization during the study period, 18 patients (Group 2, 7.2%) were hospitalized at least once for LRTI during the RSV season. The rate of moderate-severe bronchopulmonary dysplasia (BPD) was significantly higher in group 2 compared to group 1 (38.9% vs 16.2%; P=0.016). Of the 18 infants who were hospitalized, 6 (33.3%) tested positive for RSV while the remaining 12 patients (66.7%) were negative for RSV. Odds ratio (OR) analysis of several risk factors revealed the presence of BPD (OR: 3.28; 95%CI: 1.19-9), being from a family with low socioeconomic status (OR: 3.64; 95%CI 1.08-12.3) to be associated with a higher likelihood of LRTI-related hospitalization.

Conclusion

Our data demonstrated that RSV is an important LRTI agent and cause of hospitalization especially in preterm infants with additional risks such as BPD, gestational age of <28 weeks and low socioeconomic status. We suggest that improving care conditions and decreased BPD with prematurity would help in prevention of LRTI hospitalization.     

Eligibility for palivizumab prophylaxis in a cohort of children with severe bronchiolitis

In 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis. According to the 2012 AAP recommendations, 215 children (9.7%) were eligible for palivizumab prophylaxis, while 140 children (6.3%) would have been eligible based on the 2014 updated recommendations (34.9% relative decrease; 95%CI: 28.5–41.7%). The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age <29 weeks. Further development of and refinement of cost‐effective approaches for the prevention of severe RSV infection are needed.     

Appropriate prophylaxis with restrictive palivizumab regimen in preterm children in Sweden

Aim: Palivizumab (Synagis®) was registered in Sweden in 1999 for prophylaxis against respiratory syncytial virus (RSV) in premature infants. The high costs and the limited knowledge of the efficacy of this substance have led to debate about how and when it should be used. National guidelines for the use of palivizumab in Sweden were constructed in the year 2000. The aim of this study was to evaluate the guidelines. Methods: A nation-wide prospective study was conducted during the two RSV seasons of the years 2000-2002. The paediatric departments in Sweden reported the use of palivizumab, the indication for its use, and the number of infants born preterm before 36 wk of gestation and less than 2 y old who were admitted to hospital for RSV infection. Results: During the two seasons, 218 (3.8%) children who were born before 36 wk of gestation, and 97 (5.4%) who were born before 33 wk, were hospitalized because of RSV infection. Five children were treated with mechanical ventilation. No death caused by RSV was reported. A total of 390 children were treated with palivizumab, and 16 (4.1%) of those who received prophylactic treatment were admitted to hospital with RSV infection.

Conclusion: We consider the comparatively restrictive Swedish recommendations to be safe and recommend that palivizumab should also be used very restrictively in the future. In our opinion, palivizumab in preterm children could be recommended only for those with chronic lung disease younger than 1 y of age, and with active treatment for their disease.     

Guidelines for respiratory syncytial virus prophylaxis. An update

Epidemiological studies performed by the IRIS study group in the last two respiratory syncytial virus (RSV) seasons found that the hospitalization rates for RSV in premature infants born before or in week 32 of gestation were 13.4 % and 13.1 %, respectively. Of these, 18 % and 25 % of the infants were admitted to the intensive care unit. Currently available information demonstrates the efficacy of RSV monoclonal antibodies (palivizumab) and the absence of major adverse effects. To date, there are no data that indicate the need to modify the guidelines for RSV prophylaxis in premature infants published in 2000.     

Prophylaxis of respiratory syncytial virus (RSV) in preterm infants with/without bronchopulmonary dysplasia: hyperimmune globulin (RSV-IGIV) and palivizumab (MEDI-493)

Respiratory syncytial virus (RSV) causes seasonal epidemics between December and March (April) and remains the main agent that causes severe lower respiratory tract infections in young infants. Children with bronchopulmonary dysplasia up to 24 months of age and preterm infants with a gestational age of 32 weeks and below, who are less than six months of age, are at highest risk for severe RSV infection. RSV-IGIV has been demonstrated to reduce significantly RSV associated hospitalizations, RSV associated hospital days and the incidence of severe RSV lower respiratory tract infections. Monthly infusions during RSV season were safe and well tolerated. Adverse events related to the hyperimmune globulin infusion were generally mild (< 3%) including fluid overload, decreased oxygen saturation and fever. Palivizumab, an intramuscularly administered humanized monoclonal antibody (RSV-glycoprotein-F antibody), will be preferable for the future because of ease of administration and comparable reduction in the risk of hospitalization. RSV-IGIV and palivizumab are both cost expansive and prophylaxis should be limited to high-risk infants.