Medical Policy


Subject:  Prevention of Respiratory Syncytial Virus Infections
Policy #:  DRUG.00015Current Effective Date:  08/12/2013
Status:RevisedLast Review Date:  08/08/2013

Description/Scope

The goal of passive immunoprophylaxis for protection of high-risk infants and children against respiratory syncytial virus (RSV) lower respiratory tract infection is to reduce the rate of serious lower respiratory tract disease in this population. This document identifies populations at high risk for RSV and indications for RSV prophylaxis.

Position Statement

Note: RSV Season:
The U.S. Food and Drug Administration (FDA) label for immune prophylaxis for RSV with palivizumab (Synagis®) indicates that administration should occur on a monthly basis during the RSV season, which varies according to region. Specific information about national and regional RSV trends is available from the National Respiratory and Enteric Virus Surveillance System (NREVSS) at: http://www.cdc.gov/surveillance/nrevss/rsv/default.html.

Medically Necessary:

Immunoprophylaxis for respiratory syncytial virus (RSV) with intramuscular palivizumab (Synagis®) is considered medically necessary for the prevention of serious lower respiratory tract disease in infants and young children who are at high risk, when the criteria below are met:

  1. Five (5) doses of palivizumab (Synagis®) within the RSV season which begins during the first year of life are medically necessary for infants with any of the following clinical presentations:
    • Born at 28, or less, weeks of gestation (up to and including 28 weeks, 6 days) and less than 12 months of age at the start of the RSV season; OR
    • Born at 29 to 32 weeks gestation (beginning 29 weeks, 0 days through 31 weeks, 6 days) and less than 6 months of age at the start of the RSV season; OR
    • Chronic lung disease (CLD) [formerly designated Bronchopulmonary Dysplasia (BPD)] who have required medical treatment within six months before the start of the RSV season with oxygen, steroids, bronchodilators or diuretics; (Note:  Asthma, reactive airway disease and cystic fibrosis do not meet the definition of chronic lung disease in the AAP Guidelines.) OR
    • Hemodynamically significant (for example, but not limited to, receiving medication for congestive heart failure or moderate to severe pulmonary hypertension) cyanotic or acyanotic congenital heart disease (CHD); OR
    • Infants with congenital abnormalities of the airway (for example, tracheal ring) or a neuromuscular condition that compromises the handling of respiratory secretions.
  2. Up to three (3) doses of palivizumab (Synagis®) during one RSV season in the first year of life are medically necessary when ALL of the following apply:
    • Infant born between 32 and 35 weeks gestation,* (beginning 32 weeks, 0 days through 34 weeks, 6 days); AND
    • Less than 3 months of age at the start of the RSV season; AND
    • Less than 90 days old at the time of dosing; AND
    • One or more of the following risk factors are present:
      1. Attends group child care (defined as a home or facility where care is provided along with at least one other infant or young child), OR
      2. If there are siblings or other children living in the household who are less than 5 years of age. (Multiple births younger than 1 year of age do not qualify as fulfilling this risk factor.)
        *Please Note:
        Infants born between 32 and 35 weeks gestational age who meet criteria in section 1 are eligible for up to 5 doses of palivizumab (Synagis).
  3. An additional dose of palivizumab (Synagis®) is considered medically necessary for children in an approved course of treatment who undergo cardiopulmonary bypass for surgical procedures due to documented reduction in serum levels post-bypass.
  4. Completion of dosing schedule of palivizumab (Synagis®) is considered medically necessary for an infant or child who is receiving RSV immunoprophylaxis and experiences break-through RSV infection.
  5. Five (5) doses of palivizumab (Synagis®) within the RSV season during the second year of life are medically necessary for children with any of the following clinical presentations:
    • Chronic lung disease (CLD) [formerly designated Bronchopulmonary Dysplasia (BPD)] who have required medical treatment within six months before the start of the RSV season with oxygen, steroids, bronchodilators or diuretics; (Note: Asthma, reactive airway disease and cystic fibrosis do not meet the definition of chronic lung disease in the AAP guidelines.)  OR
    • Hemodynamically significant (for example, but not limited to, receiving medication for congestive heart failure or moderate to severe pulmonary hypertension) cyanotic or acyanotic congenital heart disease (CHD).
    • Infants with congenital abnormalities of the airway (for example, tracheal ring) or a neuromuscular condition that compromises the handling of respiratory secretions 

Not Medically Necessary:

Administration of more than 5 doses of palivizumab (Synagis®) in one RSV season is considered not medically necessary.

Administration of more than 3 doses of palivizumab (Synagis®) or any dose after 90 days of age is considered not medically necessary for infants born between 32 and 35 weeks gestational age unless they have a condition listed in criteria 1 above.

Immunoprophylaxis for respiratory syncytial virus is considered not medically necessary for children less than 24 months of age when the above criteria are not met.

Continued RSV immunoprophylaxis regimen with monthly doses of palivizumab (Synagis®) when the National Respiratory and Enteric Virus Surveillance System (NREVSS) epidemiologic data has confirmed that the present-year RSV season has ended is considered not medically necessary.

Investigational and Not Medically Necessary:

Immunoprophylaxis for respiratory syncytial virus is considered investigational and not medically necessary for children who reach age 24 months prior to the commencement of the RSV season.

Palivizumab (Synagis®) is considered investigational and not medically necessary for treatment in children or infants with known RSV disease except as indicated above. 

Immunoprophylaxis for respiratory syncytial virus is considered investigational and not medically necessary for infants and children with hemodynamically insignificant heart disease (e.g., secundum atrial septal defect, small ventricular septal defect, uncomplicated pulmonic stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta, and patent ductus arteriosus) who do not otherwise meet criteria above.

Immunoprophylaxis for respiratory syncytial virus is considered investigational and not medically necessary for infants and children with surgically corrected congenital heart disease unless they continue to require medication for congestive heart failure, who do not otherwise meet criteria above.

Immunoprophylaxis for respiratory syncytial virus is considered investigational and not medically necessary for all other indications not otherwise addressed as medically necessary, including, but not limited to, its use in recipients of hematopoietic stem cell transplants and individuals with cystic fibrosis who do not otherwise meet criteria above.

Rationale

Randomized placebo controlled clinical trials have demonstrated the safety and efficacy of palivizumab (Impact RSV Study, 1998) in reducing hospitalizations due to RSV infection, and in producing reductions in other measures of severity of RSV infection for infants and children younger than 24 months, with CLD or history of premature birth (children born at 32 weeks of gestation or earlier).

Palivizumab has been shown to decrease the likelihood of hospitalization due to RSV infection in infants born between 32 and 35 weeks of gestation; however, most experts agree that prophylaxis should be reserved for infants in this group who are at greatest risk. Epidemiologic data indicate that the risk of severe RSV infection most likely to require hospitalization is greater in the presence of risk factors, and the risk of severe RSV disease is a cumulative effect of the number of risk factors present.

The American Academy of Pediatrics (AAP) issued guidelines regarding the use of immune prophylaxis for RSV in the AAP Red Book 2012) and also in the 2009 publication "Policy Statement-Modified Recommendations for Use of Palivizumab for Prevention of Respiratory Syncytial Virus Infections".

The AAP Red Book was developed by members of the AAP Committee on Infectious Diseases in conjunction with the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and other leading institutions. A summary of the AAP Red Book (2012) RSV information follows:

Additional excerpted information from the AAP Red Book (2012) regarding infants born between 32 and 35 weeks' gestation is as follows:

Available data do not allow for definition of a subgroup of infants who are at risk of prolonged hospitalization and admission to the intensive care unit. Therefore, although current recommendations were designed to be consistent with the US Food and Drug Administration's approval for marketing of palivizumab for the prevention of serious RSV lower respiratory tract disease, they specifically target infants in this group with consistently identified risk factors for RSV hospitalization during the period of greatest risk, which is the first 3 months of life. Palivizumab prophylaxis should be limited to infants in this group at greatest risk of hospitalization attributable to RSV infection, namely infants younger than 3 months of age at the start of the RSV season or who are born during the RSV season and who are likely to have an increased risk of exposure to RSV. Epidemiologic data suggest that RSV infection is more likely to occur and more likely to lead to hospitalization for infants in this gestational age group when at least one of the following two risk factors is present:  a) if the infant attends child care, or b) if the infant has a sibling younger than 5 years of age. 

Prophylaxis may be considered for infants from 32 through less than 35 weeks' gestation (defined as 32 weeks, 0 days through 34 weeks, 6 days) who are born less than 3 months before the onset or during the RSV season and for whom at least 1 of the 2 risk factors (above) is present. Infants in this gestational age category should receive prophylaxis only until they reach 3 months of age and should receive a maximum of 3 monthly doses; many will receive only 1 or 2 doses until they reach 3 months of age. Once an infant has passed 90 days of age, the risk of hospitalization attributable to RSV lower respiratory tract disease is reduced. Administration of palivizumab is not recommended after 3 months of age for patients in this category.

The following guidance is contained in the AAP (2009) policy statement:   

Infants with congenital abnormalities of the airway or neuromuscular disease: Immunoprophylaxis may be considered for infants who have either significant congenital abnormalities of the airway or a neuromuscular condition that compromises handling of respiratory secretions. Infants and young children in this category should receive a maximum of 5 doses of palivizumab during the first year of life.

Infants and children with CHD: Children who are 24 months of age or younger with hemodynamically significant cyanotic or acyanotic CHD may benefit from palivizumab prophylaxis. Children younger than 24 months of age with CHD who are most likely to benefit from immunoprophylaxis include infants who are receiving medication to control congestive heart failure; infants with moderate to severe pulmonary hypertension; and infants with cyanotic heart disease.

In addition, specialty consensus agrees that up to five doses of palivizumab within each RSV season during the first 24 months of life may be applicable to infants with congenital abnormalities of the airway or neuromuscular disease.   

A multicenter, prospective, controlled, clinical trial demonstrated that palivizumab significantly reduced the rate of hospitalizations, hospital days, and days of increased oxygen usage in children with serious CHD. The data showed significantly fewer RSV-related hospital days and fewer days of increased oxygen usage, in the treated group than in the placebo group. The proportions of subjects in the placebo and palivizumab groups who experienced any adverse events were similar. Infants and children with hemodynamically insignificant heart disease were not included in this study, as they are not considered to be at increased risk from RSV. Paired palivizumab serum levels were available for 139 children before and after cardiopulmonary bypass surgery. Mean serum concentrations were reduced by 58% (98 mcg/ml [+ or -52], to 41.4 mcg/ml [+ or -33]) after bypass. Based on this observation, the authors recommended that another dose of palivizumab be administered following cardiopulmonary bypass (Feltes, 2003).

Decisions regarding prophylaxis with palivizumab in children with CHD should be made on the basis of the degree of physiologic cardiovascular compromise. The AAP Red Book (2012) guidelines suggest that the following groups of infants are not at increased risk from RSV and generally should not receive prophylaxis:

Immunoprophylaxis for RSV has not been evaluated in randomized trials for use in immunocompromised children and is, therefore, considered investigational for this population, due to lack of scientific evidence supporting health outcomes. According to the AAP Red Book (2012) guideline, although specific recommendations cannot be made, infants and young children with severe immunodeficiencies, (e.g., severe combined immunodeficiency or severe acquired immunodeficiency syndrome) may benefit from prophylaxis.

The AAP Red Book (2012) also includes the following statement:

RSV is known to be transmitted in the hospital setting and to cause serious disease in infants at high-risk. Among hospitalized infants, the major means to reduce RSV transmission is strict observance of infection control practices, including prompt initiation of precautions for RSV-infected infants. If an RSV outbreak occurs in a high-risk unit (e.g., pediatric or neonatal intensive care unit or hematopoietic stem cell transplantation unit), primary emphasis should be placed on proper infection control practices, especially hand hygiene. No data exist to support palivizumab use in controlling outbreaks of health care-associated disease, and palivizumab use is not recommended for this purpose.

Cortez and colleagues (2002) studied whether RSV-IVIg provided sufficient RSV immune prophylaxis to prevent RSV pneumonia in 54 individuals undergoing stem-cell transplantation. The authors reported a low incidence of RSV infection in the 54 RSV-IVIg subjects, as well as in 31 others not enrolled in the study, and could not determine the preventive effect of RSV-IVIg.

In reference to children with cystic fibrosis, the AAP Red Book (2012) states:

Limited studies suggest that some patients with cystic fibrosis may be at increased risk of RSV infection. Whether RSV infection exacerbates the chronic lung disease of cystic fibrosis is not known. In addition, insufficient data exist to determine the effectiveness of palivizumab use in this patient population. Therefore, a recommendation for routine prophylaxis in patients with cystic fibrosis cannot be made.

Borowitz and colleagues (2009), in an evidence review, documented guidelines for management of infants with cystic fibrosis. A recommendation was made for the use of palivizumab for RSV prophylaxis in infants with cystic fibrosis; however, there was a low certainty of net benefit reported by the authors for this particular recommendation.

During the four RSV seasons between 2000 and 2004, the Palivizumab Outcomes Registry collected data on 19,548 high risk infants who received at least one dose of palivizumab and were prospectively followed through 2004.  Ninety-one of these children had cystic fibrosis and received palivizumab as an off-label indication. Data were entered into a centralized electronic database which was maintained by the Synagis Outcomes Registry Coordinating Center where the integrity of the data was carefully maintained through such means as computerized edit checks throughout each RSV season analyzed. The confirmed RSV hospitalization rate was calculated by using only the incident RSV hospitalization within an RSV season. Hospitalizations that occurred on or before 24 hours of a subject's first injection were excluded. The hospitalization rates for children diagnosed as having cystic fibrosis were compared with historical controls from two studies that examined the incidence of hospitalization in cystic fibrosis infants with RSV infection (Abman, 1988; Armstrong, 1998). Within the observational registry data, it was noted that none of the prophylaxed infants with cystic fibrosis required hospitalization as a result of RSV infection. Compared with historical controls, the observed reduction in hospitalization found in the Registry, for those with cystic fibrosis was significant (Registry vs. Abman P = 0.0004; odds ratio 33.07; 95% confidence interval; 1.844-593.2 and Registry vs. Armstrong P = 0.0042; odds ratio 18.67; 95% confidence interval, 1.048-332.6). The authors concluded that further clinical investigation of palivizumab use in infants with cystic fibrosis seems warranted (Speer, 2008).

In a retrospective, single institution study, the medical records were reviewed for all individuals diagnosed with cystic fibrosis between the years 1997 and 2005 inclusively when the diagnosis of cystic fibrosis was confirmed before the age of 18 months. A diagnosis of cystic fibrosis was made in 76 children with data collected on 75. Of those, 40 did not receive RSV prophylaxis while 35 received palivizumab monthly during the RSV season. Among non-recipient children, 7 out of the 40 were hospitalized for acute respiratory illness during the RSV season. Of these seven children, RSV detection was positive in the nasopharyngeal secretions of three, negative in one and not requested in the others. Among the palivizumab recipient group, 3 out of 35 children were hospitalized for acute respiratory illness (P > 0.05 compared to non-recipients). Of the three palivizumab recipients who were hospitalized, RSV detection was negative in the nasopharyngeal secretions of all three. Also, amongst the hospitalized palivizumab recipients, fewer hospital days per child for their acute respiratory illness were noted (mean + SD: 0.8 + 3.07 days), as compared to hospitalized non-recipients of palivizumab (mean + SD: 1.73 + 4.27 days). However, this difference did not reach statistical significance, and the authors concluded that cystic fibrosis infants may benefit from RSV prophylaxis but that further studies are needed to determine the efficacy of this prophylaxis strategy prior to recommending implementation of an RSV prophylaxis program with palivizumab in infants with cystic fibrosis (Giebels, 2008).    

Robinson and colleagues (2012), in a Cochrane review, identified one randomized controlled trial which compared five monthly doses of palivizumab to placebo in infants up to two years of age with cystic fibrosis. The authors of the review concluded that the overall incidence of adverse events was similar in both groups and it was not possible to draw conclusions on the safety and tolerability of RSV prophylaxis and palivizumab in infants with cystic fibrosis because the trial did not specify how adverse events were classified and additional randomized studies are needed.

The manufacturers of RespiGam® (RSV IgIV) withdrew this drug from the market on March 15, 2004 citing the fact that use of Synagis in the practice community had completely replaced the need for RespiGam, as the reason for this action. Unlike palivizumab, RSV-IgIV, when it was available, was contraindicated in children with cyanotic CHD, due to safety concerns with IV administration of human immunoglobulin products.

Background/Overview

RSV is the leading cause of lower respiratory tract infection in infants and young children. Almost all children have been infected with RSV by age 2 years, and severe RSV disease requiring hospitalization occurs most commonly, among infants age 1 to 3 months. RSV is estimated to account for 57,500 annual hospitalizations among children younger than 5 years of age and accounts for approximately 1 out of every 334 hospitalizations in this age group yearly (Hall, 2009). RSV is usually transmitted by direct or close human contact. Risk factor reduction is important in the prevention of RSV. Infants should never be exposed to tobacco smoke and should be kept away from crowds and from situations in which exposure to infected individuals cannot be controlled. Participation in group childcare should be restricted, during the RSV season, for high-risk infants whenever feasible. It is especially important for caregivers to follow good hand hygiene practices.

The 2012 FDA approved label for Synagis® states:

Synagis is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease. Safety and efficacy were established in infants with bronchopulmonary dysplasia (BPD), infants with a history of premature birth (less than or equal to 35 weeks gestational age), and children with hemodynamically significant congenital heart disease (CHD). The safety and efficacy of Synagis have not been established for treatment of RSV disease.

Administration is on a monthly basis during the RSV season, and dosage is based on an individual's weight. In most seasons and regions of the United States, a total of five doses are administered, with the first dose at the beginning of November and the last dose at the beginning of March, (which will provide coverage into April). The recommendation for 5 doses is derived from the design of the clinical trials with both RespiGam and palivizumab. In the IMpact-RSV trial and in the Feltes, et al. (2003) trial involving children with hemodynamically significant CHD, 5 monthly doses of palivizumab resulted in serum concentrations greater than or equal to 37 µg/mL for more than 20 weeks in almost all subjects. One month after the fourth monthly dose of palivizumab, the mean concentration was 72 µg/mL among subjects in the Impact-RSV trial and 90 µg/mL, in the subjects in the cardiac trial. A serum concentration greater than or equal to 30 µg/mL is the proposed serologic correlate of protection, in which this concentration results in a decrease in pulmonary RSV replication by greater than 100-fold. 

The AAP (2009) policy statement reports variations in the RSV season which usually begins in November or December, peaks in January or February, and ends by March or sometime in April in the temperate climates of North America (which includes most of the United States). In equatorial countries, RSV seasons vary throughout the year. There are also variations in the RSV season in the state of Florida. Northwest Florida is consistent with most of the United States with an onset typically in mid November. In southwest or north central Florida the onset of the RSV season usually occurs in late September to early October. In southeast Florida (Miami-Dade County) the onset of the RSV season is typically in July. Alaska Native infants in southwestern Alaska have longer RSV seasons; therefore practitioners in this area may want to use CDC RSV hospitalization data to assist in determining the RSV season.

In general, practitioners may wish to use RSV data from their own region to assist in the decision-making regarding the initiation and termination of prophylaxis. The National Respiratory and Enteric Virus Surveillance System (NREVSS) is a voluntary, laboratory-based surveillance system of clinical and public health laboratories which report weekly to the Centers for Disease Control and Prevention (CDC) on the number of specimens tested and the number that tested positive for several respiratory and enteric viruses. Information on national and regional RSV trends is published by the CDC National Center for Infectious Disease and can be viewed at: http://www.cdc.gov. Because the onset of RSV activity can vary between regions and communities, physicians and health care facilities should consult their local clinical laboratories for the latest data on RSV activity. Specific information from NREVSS about national and regional RSV trends is available at: http://www.cdc.gov/surveillance/nrevss/rsv/default.html. The CDC uses RSV antigen detection data from the NREVSS to help define the RSV season. Mullins and colleagues (2003) from the CDC defined the season onset week for a given laboratory as the first of two consecutive weeks of at least 10% positive test results with at least two positive samples in the numerator of the reports of both weeks. Offset week was defined as the last of the final two consecutive weeks of at least 10% positive tests with at least two positive samples in the numerator in the reports of both weeks.

Synagis® is currently the only drug commercially available in the U.S. that is FDA-approved for prevention of RSV infections. It is postulated that use of Synagis was preferred over the formerly available RespiGam (RSV IgIV) in the practice community, due to the ease of administration, lack of interference with measles-mumps-rubella (MMR) vaccine and varicella vaccine, and lack of complications, associated with intravenous administration. 

The World Health Organization has designated RSV as a high-priority pathogen for vaccine development.  However, during the past decade, the enthusiasm for developing RSV vaccines has declined substantially, among vaccine-development companies. A combination of the inherent scientific challenges, the high-risk nature of the target populations, and the enormous cost of vaccine development probably accounts for the lower priority given to RSV vaccine programs.  Compounding the problem is a general lack of public awareness of RSV infection.

Respiratory syncytial virus infection in adults, though recognized for several decades, has been overlooked, at least in part, because of the importance of RSV in the pediatric population. A recent study has placed the public health dimensions of RSV infection in adults in perspective. Though there are no immediate clinical implications of this study, it does have important repercussions for public health strategy and for the prioritization of the development of vaccines and antiviral agents (Falsey, 2005). Palivizumab has become the standard for the prevention of RSV infection in high-risk infants; however, the agent is untested in the elderly.

Definitions

Child Care: Defined by the AAP as a home or facility where care is provided for any number of infants or young toddlers in the child care facility.

Chronic Lung Disease (CLD) and Bronchopulmonary Dysplasia (BPD): Abnormal development or growth (dysplasia) of the lungs and air passages.

Congenital Heart Disease (CHD): Heart problems present at birth.

Cyanotic: Turning pale or blue because of breathing or circulation problems; some lung or heart conditions do not allow the proper amount of oxygen to reach the blood and the body; the individual may appear very pale or even slightly blue, for example in the lips or fingers.

Ig (immune [or immuno-] globulin): An antibody, a protein made by the immune system.

Immunoprophylaxis: Prevention of disease by the use of vaccine or a serum containing antibodies.

Lower respiratory tract infection: Infection of the lungs, such as bronchiolitis or pneumonia.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  A draft of future ICD-10 Coding (effective 10/01/2014) related to this document, as it might look today, is included below for your reference. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

When services may be Medically Necessary when criteria are met: 

CPT 
90378Respiratory syncytial virus, monoclonal antibody, recombinant, for intramuscular use, 50 mg, each [Synagis]
  
HCPCS 
S9562Home injectable therapy, palivizumab, including administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
  
ICD-9 Diagnosis 
 All diagnoses
  
ICD-10 DiagnosisICD-10-CM draft codes; effective 10/01/2014:
 All diagnoses

When services are Not Medically Necessary:
For the procedure codes listed above, for the circumstances indicated in the Position Statement section as not medically necessary. 

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above when criteria are not met; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

References

Peer Reviewed Publications:

  1. Abman SH. Role of respiratory syncytial virus in early hospitalizations for respiratory distress of young infants with cystic fibrosis. J Pediatr. 1988; 113(5): 826-830.
  2. Armstrong D. Severe viral respiratory infections in infants with cystic fibrosis. Pediatr Pulmonol. 1998; 26(6): 371-379.
  3. Aujard Y, Fauroux B.  Risk factors for severe respiratory syncytial virus infection in infants. Resp Med. 2002; 96(Suppl B):S9-S14.
  4. Black CP. Systematic review of the biology and medical management of respiratory syncytial virus infection. Respir Care. 2003; 48(3):209-231.
  5. Boeckh M, Berry MM, Bowden RA, et al. Phase I evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants. J Infect Dis. 2001; 184(3):350-354.
  6. Cohen SA, Zanni R, Cohen A, et al. Palivizumab Outcomes Registry Group. Palivizumab use in subjects with congenital heart disease: results from the 2000-2004 Palivizumab Outcomes Registry. Pediatr Cardiol. 2008; 29(2):382-387.
  7. Cortez K, Murphy BR, Almeida KN, et al. Immune-globulin prophylaxis of respiratory syncytial virus infection in patients undergoing stem-cell transplantation. J Infect Dis 2002; 186(6):834-838.
  8. Cystic Fibrosis Foundation, Borowitz D, Robinson KA, Rosenfeld M, Davis SD, et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009; 155(6 Suppl):S73-93.
  9. DeVincenzo JP, Hirsch RL, Fuentes RJ, Top FH, Jr. Respiratory syncytial virus immune globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone marrow transplantation - a compassionate use experience. Bone Marrow Transplant. 2000; 25(2):161-165.
  10. Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in elderly and high-risk adults. NEJM. 2005; 352(17):1749-1759.
  11. Feltes TM, Cabala AK, Meissner HC, et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr. 2003; 143(4):532-540.
  12. Fenton C, Scott LJ, Plosker GL. Palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection. Paediatr Drugs. 2004; 6(3):177-197.
  13. Ghosh S. Champlin RE, Ueno NT, et al. Respiratory syncytial virus infections in autologous blood and marrow transplant recipients with breast cancer: combination therapy with aerosolized ribavirin and parenteral immunoglobulins. Bone Marrow Transplant. 2001; 28(3):271-275.
  14. Giebels K, Marcotte JE, Podoba J, et al. Prophylaxis against respiratory syncytial virus in young children with cystic fibrosis. Ped Pulmonol. 2008; 43:169-174.
  15. Greenough A, Thomas M. Respiratory syncytial virus prevention: past and present strategies. Expert Opin Pharmacother. 2000; 1(6):1195-1201.
  16. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009; 360(6):588-598.
  17. Lambert AL, Mangum JB, DeLorme MP, Everitt JI. Ultrafine carbon black particles enhance respiratory syncytial virus-induced airway reactivity, pulmonary inflammation, and chemokine expression. Toxicol Sci. 2003; 72(2):339-346.
  18. Levy BT, Graber MA. Respiratory syncytial virus infections in infants and young children. J Fam Pract. 1997; 45:473-481.
  19. Meissner HC. Selected populations at increased risk from respiratory syncytial virus infection. Pediatr Infect Dis J. 2003; 22:S40-S45.
  20. Meissner HC, Anderson LJ, Pickering LK. Annual variation in respiratory syncytial virus season and decisions regarding immunoprophylaxis with palivizumab. Pediatrics. 2004; 114(4); 1082-1084.
  21. Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, Quero J. IRIS Study Group. Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J. 2003; 22(9):823-827.
  22. Polack FP, Karron RA. The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J. 2004; 23(1 Suppl):S65-S73.
  23. Robinson RF, Nahata MC. Respiratory syncytial virus (RSV) immune globulin and palivizumab for prevention of RSV infection. Am J Health Syst Pharm. 2000; 57(3):259-264.
  24. Rodriguez WJ, Gruber WC, Groothuis JR, et al. Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children. Pediatrics. 1997; 100(6):937-942.
  25. Rodriguez WJ, Gruber WC, Welliver RC, et al. Respiratory syncytial virus (RSV) immune globulin intravenous therapy for RSV lower respiratory tract infection in infants and young children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin Study Group. Pediatrics. 1997; 99(3): 454-461.
  26. Simoes EA, Sondheimer HM, Top FH, Jr, et al. Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. J Pediatr. 1998; 133(4):492-499.
  27. Simoes EA. Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease.  J Pediatr. 2003; 143:S118-S126.
  28. Sondheimer HM, Cabalka AK, Feltes TF, et al. Palivizumab (PV) reduces hospitalization due to respiratory syncytial virus in young children with serious congenital heart disease. Pediatr Cardiol. 2002; 23(6):664.
  29. Speer ME, Fernandes CJ, Boron M, Groothuis JR. Use of Palivizumab for prevention of hospitalization as a result of respiratory syncytial virus in infants with cystic fibrosis. Ped Infect Dis J. 2008; 27(6):559-561.
  30. Strutton DR, Stang PE. Prophylaxis against respiratory syncytial virus (RSV), varicella, and pneumococcal infections: economic-based decision-making. J Pediatr. 2003; 143(5 Suppl):S157-S162.
  31. The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998; 102(3 Pt 1):531-537.
  32. The PREVENT Study Group: Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics. 1997; 99(1):93-99.
  33. Wu H, Pfarr DS, Losonsky GA, et al. Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Agency for Healthcare Research and Quality (AHRQ). Management of Bronchiolitis in Infants and Children. Evidence Report/Technology Assessment No. 69. Rockville, MD: Agency for Healthcare Research and Quality. 2003. AHRQ Publication No. 03-E014.
  2. American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. American Academy of Pediatrics with endorsement from the American Academy of Family Physicians, the American Thoracic Society, the American College of Chest Physicians, and the European Respiratory Society. Pediatrics. 2006; 118(4):1774-1793. Available at: http://pediatrics.aappublications.org/cgi/reprint/118/4/1774. Accessed on June 20, 2013.
  3. American Academy of Pediatrics (AAP). 2012 Red Book Online. Section 3: Summaries of Infectious Diseases. Respiratory Syncytial Virus (RSV). Report of the Committee on Infectious Diseases. Elk Grove Village, IL: AAP; 2012.
  4. American Hospital Formulary Service® (AHFS). AHFS Drug Information 2013®. Bethesda, MD: American Society of Health-System Pharmacists®, 2013. 
  5. Canadian Agency for Drugs and Technologies in Health (CADTH), formerly known as the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) Technology Report: Palivizumab Prophylaxis against Respiratory Syncytial Virus. Ottawa, ON. Issue 80; March 2007. Available at: http://www.cadth.ca/media/pdf/I3006_tr_Palivizumab_e.pdf. Accessed on June 20, 2013.
  6. Centers for Disease Control and Prevention. Respiratory Syncytial Virus Activity – United States 2005-2006. MMWR. 2006; 55(47):1277-1279.
  7. Centers for Disease Control and Prevention. Respiratory Syncytial Virus Activity – United States 2000-2001 Season. MMWR. 2002; 51(2):26-28.
  8. Committee on Infectious Diseases. From the American Academy of Pediatrics: Policy Statement--Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009; 124(6):1694-1701. Available at: http://pediatrics.aappublications.org/cgi/reprint/124/6/1694. Accessed on June 20, 2013.
  9. Flynn E, Matz P, Woolf A, Wright R. Indoor Air Pollutants Affecting Child Health. A project of the American College of Medical Toxicology. 2000 Nov.
  10. Fuller H, Del Mar C. Immunoglobulin treatment for respiratory syncytial virus infection. Cochrane Database Systematic Rev. 2004; CD004883.
  11. Infectious Diseases and Immunization Committee, Canadian Pediatric Society. Use of Palivizumab in children with congenital heart disease. Pediatr Child Health 2003; 8(10):632-633.
  12. Meissner HC, Long SS. and the American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics. 2003; 112(6):1442-1446 and Technical Report: 1447-1452.
  13. Mullins JA, Lamonte AC, Bresee JS, et al. Substantial variability in community respiratory syncytial virus season timing. Pediatr Infect Dis J. 2003; 22:857-862.
  14. Palivizumab. In: DrugPoints® System [electronic version]. Truven Health Analytics, Greenwood Village, CO. Updated April 25, 2012. Available at: http://www.micromedexsolutions.com. Accessed on June 20, 2013.
  15. Robinson KA., Odelola OA, Saldanha I, Mckoy N. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis. Cochrane Database of Systematic Reviews 2012; 2:CD007743.
  16. Synagis® [Product Information], Gaithersburg, MD. MedImmune, LLC; April 2013. Available at: http://www.medimmune.com/pdf/products/synagis_pi.pdf. Accessed on June 20, 2013.
  17. Wang D, Cummins C, Bayliss S, et al. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation. Health Technol Assess. 2008; 12(36):iii, ix-x, 1-86.
Web Sites for Additional Information
  1. The National Respiratory and Enteric Virus Surveillance System (NREVSS). Available at: http://www.cdc.gov/surveillance/nrevss/. Accessed on June 20, 2013.
Index

Bronchopulmonary Dysplasia
Chronic Lung Disease
Palivizumab
Synagis®

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

Revised08/08/2013Medical Policy & Technology Assessment Committee (MPTAC) review. Position statement clarified regarding other siblings in the home. Rationale and Reference sections updated.
Revised08/09/2012MPTAC review. Note in position statement clarified. Position statement #2 removed and integrated into #1 and #6 (now #5). Rationale, Background and Reference sections updated.
Revised08/18/2011MPTAC review. Clarified investigational and not medically necessary statements for hemodynamically insignificant heart disease and for surgically corrected congenital heart disease with the addition of the wording "who do not otherwise meet criteria above." Revised medically necessary statement for infants with congenital abnormalities of the airway or a neuromuscular condition that compromises handling of respiratory secretions. Rationale, Background, Definition, and Reference sections updated.
Reviewed08/19/2010MPTAC review. Description, Note in position statement, Rationale, Background, References, and Index updated.
 01/01/2010Updated Coding section with 01/01/2010 CPT/HCPCS changes; removed codes 90379 and J1565 deleted 12/31/2009.
Revised08/27/2009MPTAC review. The criteria for RSV prophylyaxis were revised for premature infants born between 32 and 35 weeks' and for infants with congenital abnormalities of the airway or neuromuscular disease who were born before 35 weeks of gestation who have either congenital abnormalities of the airway or a neuromuscular condition that compromises handling of respiratory secretions. The Rationale section has been updated with information about the 2009 updated Red Book recommendations from the American Academy of Pediatrics (AAP). The descriptions of gestational age within the medical necessity criteria for premature infants have been revised consistent with the AAP update. References were updated.
Revised11/20/2008MPTAC review. The medically necessary criteria for use of Synagis in premature infants was clarified to indicate that infants born at 28, or less, weeks of gestation (up to and including 28 weeks, 0 days) may benefit if they are less than 12 months of age at the start of the RSV season; or infants born at 29 to 32 weeks gestation (beginning 28 weeks, 1 day through 32 weeks, 0 days) may benefit if they are less than 6 months of age at the start of the RSV season; and infants born between 32 and 35 weeks gestation, (beginning 32 weeks, 1 day through 35 weeks, 0 days) may benefit if they are less than 6 months of age at the start of the RSV season and have 2 or more risk factors. An additional position statement was added to clarify that continued monthly doses of palivizumab beyond the end of the present-year RSV season is considered not medically necessary. Also, the investigational and not medically necessary position statement was revised to add the following: cystic fibrosis patients without reduced lung reserve and the separate position statement was clarified regarding children aged 24 months or older at the start of the RSV season as being considered investigational and not medically necessary. Rationale and References were also updated.
Revised11/29/2007MPTAC review. Information was added to the medical necessity criteria under hemodynamically significant congenital heart disease (CHD) recommending a dose of palivizumab for children who undergo cardiopulmonary bypass, to be given as soon as possible post-bypass. A new statement was added under the "Not Medically Necessary" section as follows: Immunoprophylaxis for RSV is considered not medically necessary for children less than 24 months of age when criteria are not met. A new statement was also added to the "Investigational and Not Medically Necessary" section as follows: Immunoprophylaxis for RSV is considered investigational and not medically necessary for children ages 24 months or older when criteria are not met. The phrase "investigational/not medically necessary" was clarified to read "investigational and not medically necessary." Information was also added to the Background section for clarification of the definition of RSV prevalence in a given community. References were updated.
Revised08/23/2007MPTAC review. Minor revisions were made to the medical necessity criteria for clarification regarding reduced lung reserve patients requiring medical treatment within six months before the start of the RSV Season and for premature candidates exposed to environmental air pollutants within the home. The investigational/not medically necessary statement regarding children/infants with known disease was also clarified to refer to treatment, not prophylaxis (which was the former language).  Information was also clarified within the 'Background/Overview' section regarding the recommended serum concentration level (changed from 40 ug/mL to 30 ug/mL taken from the Impact-RSV trial) and the recommendation that once a child meets criteria for treatment with Synagis, administration should continue throughout the season and not stop at the point that the infant reaches either six or 12 months of age (taken from the 2006 AAP Red Book).
Reviewed05/17/2007MPTAC review. No change to criteria.  References were updated.
Revised06/08/2006MPTAC review. Revision made to Position statement to remove reference to RespiGam which is no longer available. References also updated
Revised07/14/2005MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.
Pre-Merger Organizations

Last Review Date

Document Number

Title

Anthem, Inc.

 

09/30/2004DRUG.00015Prevention of Respiratory Syncytial Virus Infections
WellPoint Health Networks, Inc.06/24/20048.05.01Immune Prophylaxis for Respiratory Syncytial Virus