RECORD STATUS: None CITATION: Oertel M, Driver L. Palivizumab. University HealthSystem Consortium (UHC). Drug Monograph. 2000

OBJECTIVE: Palivizumab is a prophylactic therapy shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations but has a high acquisition cost. The objective was to systematically examine the cost effectiveness of palivizumab in defined infant groups and identify important cost and outcome determinants. METHODS: Literature searches of MedLine, the Cost-Effectiveness Analysis registry and the UK NHS Economic Evaluation Database (NHS EED) were conducted to identify economic evaluations of palivizumab compared to no prophylactic treatment for RSV prevention in any infant population. Study quality was evaluated using Quality of Health Economic Studies (QHES) criteria and results converted to 2009 CAN$ for comparison. RESULTS: A total of 23 articles meeting inclusion criteria were identified, including 11 cost-utility analyses (CUAs) and 12 cost-effectiveness analyses (CEAs). Quality of individual analyses was fairly high (range 60-100, median 86). Results ranged from cost dominance for prophylaxis to $3,365,769/QALY depending on population, outcome measures, and input parameters. Base-case and sensitivity-analysis mortality rates varied between studies and influenced results. CONCLUSIONS: RSV prophylaxis with palivizumab is cost effective in specific groups of high-risk infants, especially those with multiple environmental risk factors. Cost-effectiveness estimates vary between populations and settings and are more positive in those at highest risk for RSV hospitalization. LIMITATIONS: Direct comparison of the published reports was limited by restriction to English language articles and the varied methodologies, input measures, and populations across the studies reviewed. Although reported currencies were converted to a common unit for comparison, this does not completely account for monetary and inflation differences.

RECORD STATUS: None CITATION: Canadian Coordinating Office for Health Technology Assessment. Palivizumab (Synagis) Canadian Coordinating Office for Health Technology Assessment (CCOHTA). 2003

Respiratory syncytial virus infection is an important cause of morbidity. Although palivizumab prophylaxis is widely used, it is uncertain whether the cost is justified. A systematic review was therefore performed of the safety, efficacy, and the likely cost effectiveness of prophylaxis for preterm infants in the United Kingdom using a standard search strategy. The only randomised controlled trial identified showed a reduction in hospital admission but no benefit on more serious outcomes. None of the United Kingdom cost studies showed economic benefit for palivizumab prophylaxis. New treatments are rarely cost effective, and, in the absence of a comprehensive economic assessment, continued use for high risk infants may appear justified.

ANTECEDENTES: El palivizumab ha demostrado su eficacia para profilaxis del virus respiratorio sincicial (VRS) en niños con prematuridad o enfermedad cardiaca congénita. A pesar de la escasez de datos, el palivizumab es a veces utilizado para prevenir la progresión cuando pacientes de alto riesgo se presentan con una infección del tracto respiratorio superior (IRA) por VRS, o como terapia cuando algunos pacientes se presentan con una infección grave de las vías respiratorias bajas (IRB) por VRS. MÉTODOS: Se llevó a cabo una revisión sistemática de la literatura sobre el uso de palivizumab como terapia para el VRS. Los desenlaces primarios fueron la progresión de IRA a IRB y las tasas de supervivencia. Los desenlaces secundarios fueron los eventos adversos debidos al palivizumab, los niveles plasmáticos de palivizumab, y la concentración de VRS en secreciones respiratorias. RESULTADOS: La búsqueda arrojó 1 eporte de caso, 4 series de casos, y 2 ensayos controlados aleatorizados (ECA), con un total de 136 adultos y niños. Los ECA no fueron suficientes para ver los desenlaces clínicos. Mediante la combinación de todos los desenlaces clínicos informados, 3 (12%) de 25 pacientes con IRA que recibieron palivizumab murieron de VRS y 5 de 88 pacientes con IRB en el momento del tratamiento murieron de VRS (6%). Los niveles de palivizumab parecieron ser adecuados por al menos 3 semanas desde la inyección intravenosa con 15 mg/kg. La terapia resultó en la disminución de las concentraciones de VRS en secreciones traqueales. CONCLUSIÓN: ECA más grandes serán requeridos antes de poder recomendar palivizumab como terapia para el VRS en cualquier situación clínica.

BACKGROUND: Palivizumab is indicated for respiratory syncytial virus (RSV) prophylaxis in high-risk children. However, relatively little is known about the current use, compliance, and outcomes associated with this medication. METHODS: A prospective, observational, registry based on 27 sites, with monthly follow-up of infants at high risk for RSV who received at least 1 dose of palivizumab during the 2005-2009 RSV seasons. RESULTS: A total of 5286 children were enrolled (56.6% male; 71.7% white; average gestational age, 32.1 ± 5.5 weeks). Of them, 3741 patients (70.8%) were prophylaxed for prematurity only, 449 (8.5%) for bronchopulmonary dysplasia/chronic lung disease, 508 (9.6%) for congenital heart disease, and 588 (11.1%) for other reasons. Overall, 19,485 doses were given. On average, infants received 86.0% ± 28.4% of their expected number of injections; 71.2% of infants received their injections in the recommended time periods. Of the 5286 participants enrolled, 308 patients were hospitalized for respiratory tract illness (hospitalization rate, 5.8%). The RSV-hospitalization rate was calculated as 1.38%. Having siblings increased likelihood of hospitalization (66.9% vs. 55.7%, P < 0.005), and was significantly correlated with time to hospitalization in this cohort (P = 0.050). CONCLUSIONS: The overall RSV-hospitalization rate in our study was within the range found in previous reports (1.3%-5.3%), although it did not mimic the declining rates of the US Palivizumab Outcomes Registry. This could be due to increased testing for RSV when hospitalized and increasing rates of prophylaxis of infants with underlying medical disorders.

Respiratory syncytial virus is the most common cause of bronchiolitis, a lower respiratory tract infection occurring in infancy. It is responsible for several rehospitalizations, substantial morbidity and occasional deaths in the UK every year. Palivizumab is a recombinant monoclonal antibody that has been shown to reduce hospitalizations in infected infants. It is licensed for high-risk infants, primarily those born pre-term or with chronic pulmonary or cardiac conditions. Palivizumab is expensive, but several economic analyses have determined highly discrepant costs. This article reviews the limitations of the available efficacy and economic data, and highlights problems in interpretation and extrapolation. We also present the results of a cost-effectiveness analysis relevant to populations of high-risk infants in the UK.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children, accounting for approximately 75,000-125,000 hospitalizations per year. It is estimated that in 2000, RSV infection accounted for 1.7 million office visits, 402,000 emergency room visits, and 236,000 hospital outpatient visits per year for children younger than 5 years of age. Palivizumab, a humanized monoclonal antibody directed against RSV, is the only immunoprophylaxis therapy approved by the FDA for prevention of serious lower respiratory tract disease caused by RSV in infants (up to 2 years of age) who meet 1 or more of the following criteria for high risk: (a) gestational age up to 35 weeks;(b) diagnosis of chronic lung disease (CLD, formerly bronchopulmonary dysplasia [BPD]); or (c) diagnosis of cyanotic or complex congenital heart disease. The RSV season typically occurs between November and March but may vary by region. During the period of our review, depending on local duration of the RSV season, infants usually required 5 monthly (every 28-30 days) intramuscular injections of palivizumab. Infants born in the middle of the season received their palivizumab doses from the time of birth to the end of the season and, therefore, may have required less than 5 doses.It is unclear if compliance with monthly doses is a problem and whether noncompliance increases the risk of RSV hospitalizations in routine clinical practice. OBJECTIVES: To (a) identify and describe compliance rates and the factors that influence parental compliance with immunoprophylaxis regimens, (b)review intervention programs and describe those that have been associated with increased compliance, and (c) summarize the association of compliance with RSV hospitalization rates. METHODS: An electronic literature search was conducted using journal databases, including Ovid, Current Contents, Embase, Medline In-Process & Other Non-Indexed Citations; Ovid Medline, PubMed, and Web of Science;and an abstract database, Medical Intelligence Solution, for citations through April 2008. Specific search terms used were palivizumab with patient compliance, patient adherence, or patient persistence. RESULTS: Twenty-five articles and abstracts met the inclusion criteria. Available studies were mostly retrospective or observational prospective.Compliance, defined in various ways across the studies, varied between 25% and 100%, and 12 studies identified some of the factors related to noncompliance. Compliance generally was lower among Medicaid patients,African American patients, and other minorities. Ten studies (3 manuscripts and 7 abstracts) investigated the association of administration of prophylaxis through monthly home visits by a health professional with parental compliance with therapy. Most of the home-based programs were associated with higher compliance rates compared with clinic or office programs.Rates as high as 94% and 64% were achieved when Medicaid infants and infants of minority descent, respectively, received their doses through a home health program. When these infants received their doses at a clinic or office, depending on the definition of compliance, rates were 61%-100% for Medicaid infants and 44% for infants of minority descent. Reminder telephone calls to parents or caregivers, comprehensive multidisciplinary programs that included extensive counseling of parents, calendars with sticker reminders, and education in the language native to parents also were associated with increased compliance, although statistical significance was reported in only 1 study. Several studies recommended educating parents on the benefits of RSV prophylaxis, alleviating transportation and language difficulties, recognizing cultural differences and biases, and clarifying misperception of RSV illness severity. Home health programs had lower rates of RSV hospitalizations than office-based programs in 3 analyses conducted in 2 studies. In 4 other abstracts, the rates of RSV hospitalization for home health programs and office-based administration did not significantly differ. In a large, 4-season, prospective outcome study, compliant infants had lower RSV hospitalization rates than those who were not compliant under one definition of compliance (doses within 35-day intervals). RSV hospitalization rates were not significantly different using another definition of compliance (receipt of anticipated doses, expected vs. observed rates).In a large survey of 10,390 infants identified from pharmacy dispensing records, RSV hospitalization rates were 1.4% in the compliant group versus 3.1% in the noncompliant group (OR = 2.2, 95% CI = 1.4-3.5, P < 0.001).Adjustment for confounding was not reported in these studies. CONCLUSION: Medicaid and minority infants were less likely to receive scheduled palivizumab doses. Home-based programs for the administration of palivizumab have been investigated more than other interventions and are associated with improved compliance compared with office-based administration. Compliance with dosing, in general, was associated with lower RSV hospitalization rates. However, these strategies should be further investigated using well-designed studies.

OBJECTIVE: To review and summarize the literature concerning the cost-effectiveness of palivizumab compared to no prophylaxis in infants and young children with congenital heart disease (CHD). METHODS: A systematic literature search (MEDLINE to March 2012, limited to English language) identified studies that examined the cost-effectiveness of palivizumab in CHD populations. The quality of each study was assigned a quality score of 1-100 based on the Quality of Health Economic Studies (QHES) instrument. RESULTS: Ten studies were identified through the search strategy, of which four principally addressed the research question and six additional articles examined CHD in conjunction with other high-risk indications for palivizumab in their economic analyses. QHES for the studies ranged from 58-100, with a median score of 93 (76 for principal articles, 94 for secondary analyses). Cost-utility analyses, which evaluated costs per quality-adjusted life year (QALY), showed favorable results in five analyses (range $10,329-$16,648 per QALY), while the other two suggested no cost-effectiveness ($146,061 and $169,971 per QALY). Of three cost-effectiveness analyses, which assessed costs per hospital admission prevented (HAP), two concluded that the drug was not cost-effective ($16,216/day of hospitalization prevented and $868,296/HAP), while one did not interpret the final result ($43,561/HAP). LIMITATIONS: Significant variance exists across study characteristics, analytic models utilized, duration of RSV seasons assessed, primary outcome measures evaluated, sensitivity analyses conducted, and other model assumptions. Further, it was difficult to obtain true CHD-based quality scores for the studies that analyzed more than one indication. CONCLUSIONS: The findings of this review currently remain inconclusive. Although a favorable trend was identified in the cost-utility analyses, additional rigorously conducted studies are necessary to better estimate the cost-effectiveness of palivizumab for CHD infants in clinical practice.

Palivizumab prophylaxis has been demonstrated to reduce the number of hospitalizations attributable to respiratory syncytial virus in high-risk infants. However, as palivizumab acquisition costs are high, quantifying cost-effectiveness is important. The primary aim of this review was to examine the cost-effectiveness of palivizumab across numerous indications in high-risk infants and to report on factors that may impact outcomes. A systematic literature search was conducted to identify pharmacoeconomic analyzes of palivizumab compared to no prophylaxis for respiratory syncytial virus in infants and young children. A total of 28 articles met inclusion criteria and were subsequently assigned quality scores according to the Quality of Health Economic Studies criteria. Results varied according to perspective, input parameters, outcome measures, populations and base-case and sensitivity analyses. Overall, cost-effectiveness results were inconsistent. Some studies reported favorable outcomes, while others did not, or were inconclusive. Factors to consider in the interpretation of such economic evaluations are discussed.