Commercial

Immune Prophylaxis for Respiratory Syncytial Virus (RSV)
08.00.22o

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Immune prophylaxis using palivizumab (Synagis) is considered medically necessary and, therefore, covered for a maximum of five doses in an annual respiratory syncytial virus (RSV) season for the prevention of serious lower respiratory tract infection caused by RSV in the following high-risk individuals, when the criteria for the indications listed below are met:
  • Chronic lung disease (CLD) of prematurity
    • Infants and children younger than 24 months of age with chronic lung disease (CLD) of prematurity who were born at a gestational age of less than 32 weeks, 0 days and required more than 21 percent oxygen for at least the first 28 days after birth:
      • During the first year of life
      • During the second year of life for individuals who require medical therapy for CLD within the six months before the start of the RSV season. (Medical therapy includes any of the following: a requirement for supplemental oxygen, diuretics, or corticosteroids)
  • Congenital abnormalities of the airway or certain neuromuscular diseases
    • Infants and children 12 months of age or younger at the start of the RSV season with either of the following indications:
      • Congenital abnormalities of the airway
      • Neuromuscular disease that compromises mobilization of respiratory secretions
  • Congenital heart disease (CHD)
    • Infants and children with congenital heart disease (CHD) younger than 12 months of age at the start of the RSV season who meet any of the following criteria:
      • Hemodynamically significant acyanotic CHD, when the individual is receiving medication to control congestive heart failure and will require cardiac surgical procedures
      • Hemodynamically significant cyanotic CHD, after consultation with a pediatric cardiologist
      • Diagnosis of moderate-to-severe pulmonary hypertension
  • Cystic fibrosis with nutritional compromise and/or chronic lung disease (CLD)
    • ​Infants and children younger than 24 months of age with cystic fibrosis who have nutritional compromise and/or manifestations of severe lung disease (previous hospitalizations for pulmonary exacerbation in the first year of life or abnormalities on chest radiography or chest computed tomography that persists when stable)
  • Immunocompromised status
    • Infants and children younger than 24 months of age who are profoundly immunocompromised (eg, due to transplantation or chemotherapy) during the RSV season
  • Prematurity
    • Infants and children born before 29 weeks gestation (29 weeks, 0 days) who are younger than 12 months of age at the start of the RSV season
An additional postoperative dose of palivizumab (Synagis) is considered medically necessary and, therefore, covered for infants or children younger than 24 months of age who are currently receiving palivizumab (Synagis) when they are medically stable, meet the above criteria for immune prophylaxis, and have undergone one of the following procedures during the current RSV season:
  • Surgical procedures that use cardiopulmonary bypass
  • Cardiac transplantation
According to the American Academy of Pediatrics (2021), Respiratory Syncytial Virus (RSV) season onset can be determined in real time by identifying the first week of two consecutive weeks that RSV real time-polymerase chain reaction (RT-PCR) test positivity is three percent or greater or antigen detection positivity is 10 percent or greater. Because five monthly doses of palivizumab will provide more than six months of serum palivizumab (Synagis) concentrations above the threshold for protection for most infants, administration of more than five monthly doses is not recommended within the continental US. For qualifying infants born during the RSV season, fewer than five doses will be needed to provide protection until the RSV season ends in their region.

Medical necessity criteria for immune prophylaxis for RSV in at-risk infants and young children are subject to change based on updated recommendations as outlined in the AAP policy statement and Red Book.

NOT MEDICALLY NECESSARY

If an infant or child receiving monthly prophylaxis with palivizumab (Synagis) experiences a breakthrough RSV hospitalization, monthly prophylaxis with palivizumab (Synagis) is not medically necessary, and therefore not covered, due to the low likelihood of a second RSV hospitalization in the same season.

EXPERIMENTAL/INVESTIGATIONAL

All other indications for palivizumab (Synagis) are considered experimental/investigational and, therefore, not covered.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

The Company-contracted providers must obtain palivizumab (Synagis) through the Medical Benefit Direct Ship Program vendor, whereby a contracted vendor ships the agent directly to the Company-contracted provider. A Medical Benefit Direct Ship vendor ships palivizumab (Synagis) to the Company-contracted provider's office as medically appropriate. The vendor submits the authorized claim and is reimbursed directly for the product. The Company-contracted providers will not receive reimbursement for the actual pharmaceutical.

Administration of palivizumab (Synagis) is eligible for reimbursement when administered in the professional provider's office. Administration of palivizumab (Synagis) in the home setting is only eligible for reimbursement for members who are receiving skilled nursing services by a home health care agency for a separate indication.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, palivizumab (Synagis) is covered under the medical benefits of the Company’s products when the medical necessity criteria in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Palivizumab (Synagis) was approved by the FDA on June 15, 1998, for the use of prophylaxis of serious respiratory tract disease caused by respiratory syncytial virus (RSV)​ in pediatric individuals at high risk.

DOSING AND ADMINISTRATION

According to the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP), a maximum of five doses of palivizumab (Synagis) is generally sufficient to provide immune prophylaxis for RSV during the high-risk period (the beginning of November through the beginning of March) in all geographic areas. (Note: Infants born during the RSV season will be eligible for less than five monthly doses of palivizumab [Synagis]). It may be eligible earlier than November or later than March, depending on seasonal and regional trends. These trends are concurrently reviewed based on information from public health authorities such as the National Respiratory and Enteric Virus Surveillance System (NREVSS) that monitors temporal and geographic patterns associated with the detection of RSV, among other infectious diseases. Participating laboratories report virus detections, isolations, and electron microscopy results on a weekly basis. NREVSS data is integrated with the CDC to help define the RSV season.

In accordance with FDA-approved labeling, palivizumab (Synagis) is administered intramuscularly in a dose of 15 mg/kg every 30 days during the RSV season.

Palivizumab (Synagis) is eligible for administration in the home setting by a home health care agency for individuals who are receiving skilled nursing services for a separate indication.

Description

Each year in the United States, respiratory syncytial virus (RSV) causes hospitalizations in two to three percent of infants in the first 12 months of life. Although RSV infection is largely self-limiting, certain populations may be at an increased risk for complications.

Palivizumab (Synagis) (MedImmune; Gaithersburg, MD) is a humanized monoclonal antibody that is produced by recombinant ​deoxyribonucleic acid (DNA) technology. Palivizumab (Synagis) was licensed in June 1998 by the ​US Food and Drug Administration ​(FDA) and "is indicated for the prevention of serious lower respiratory tract disease caused by RSV in children at high risk of RSV disease.” In the absence of a specific definition of “high risk” by the FDA, the American Academy of Pediatrics (AAP) has endeavored to provide pediatricians and other professional providers with more precise guidance for determining who is at increased risk since palivizumab (Synagis)​ was first licensed. The FDA label has subsequently been updated to better define the appropriate pediatric population to receive palivizumab (Synagis).

Palivizumab (Synagis) is indicated for use in high-risk infants and children younger than 24 months of age with chronic lung disease (CLD) of prematurity, which is defined by the AAP as an individual with a gestational age less than 32 weeks, 0 days who required more than 21 percent oxygen for at least the first 28 days after birth.

Infants with neuromuscular disease or congenital anomaly that impairs the ability to clear secretions from the upper airway because of ineffective cough are known to be at risk for a prolonged hospitalization related to lower respiratory tract infection and, therefore, may be considered for prophylaxis with palivizumab (Synagis) during the first year of life.

Among the patient-specific parameters, the American Academy of Pediatrics (AAP) recommends the prophylactic use of palivizumab (Synagis) in selected individuals under 12 months of age who are born within 12 months of onset of the RSV season and have hemodynamically significant congenital heart disease (CHD). The recommendation suggests that prophylactic use of palivizumab (Synagis) should be administered for the following conditions:
  • Acyanotic CHD in individuals who are receiving medication to control congestive heart failure and will require cardiac surgical procedures
  • Moderate-to-severe pulmonary hypertension
  • Cyanotic CHD, after consultation with a pediatric cardiologist
The AAP also recommends a postoperative dose of palivizumab (Synagis) for infants or children younger than 24 months who are currently receiving palivizumab (Synagis) and have undergone cardiac transplantation or a surgical procedure that uses cardiopulmonary bypass. This recommendation is based on evidence suggesting that there is a significant intraoperative loss of serum palivizumab (Synagis) levels.

The following groups of infants with CHD are not at increased risk of RSV infection and generally should not receive immunoprophylaxis:
  • Infants and children with hemodynamically insignificant heart disease (eg, secundum atrial septal defect, small ventricular septal defect, pulmonic stenosis, uncomplicated aortic stenosis, mild coarctation of the aorta, and patent ductus arteriosus)
  • Infants with lesions adequately corrected by surgery, unless they continue to require medication for congestive heart failure
  • Infants with mild cardiomyopathy who are not receiving medical therapy for the condition
  • Children in the second year of life
The AAP has stated that routine use of palivizumab (Synagis) prophylaxis in patients with cystic fibrosis, including neonates diagnosed with cystic fibrosis by newborn screening, is not recommended unless other indications are present.

Palivizumab (Synagis) prophylaxis has not been evaluated in randomized trials in the immunosuppressed population; however, the AAP suggests that children with severe immunodeficiencies may benefit from immune prophylaxis.

Lastly, the AAP recommends prophylaxis with palivizumab (Synagis) for those born prematurely at less than 29 weeks gestational age.

There is limited data to suggest a slight increase in RSV hospitalization rates among children with Down syndrome. However, data is insufficient to justify a recommendation for routine use of prophylaxis with palivizumab (Synagis) in children with Down syndrome unless qualifying heart disease, CLD, airway clearance issues, or prematurity (<29 weeks, 0 days gestation) is present.

Hospitalization rates attributable to RSV decrease during the second RSV season for all children. A second season of palivizumab prophylaxis is recommended only for preterm infants born at <32 weeks, 0 days gestation who required at least 28 days of oxygen after birth and who continue to require supplemental oxygen, diuretics, or chronic systemic corticosteroid therapy, within six months of the start of the second RSV season.

If any infant or young child receiving monthly palivizumab prophylaxis experiences a breakthrough RSV hospitalization, monthly prophylaxis should be discontinued because of the extremely low likelihood of a second RSV hospitalization in the same season (<0.5 percent).

RSV SEASON AND IMMUNE PROPHYLAXIS

According to peer-reviewed literature, five monthly doses of palivizumab at 15 mg/kg per dose will provide more than six months (>24 weeks) of serum palivizumab concentrations above the desired level for most children; therefore, administration of more than five monthly doses is not recommended within the continental United States. For qualifying infants who require ​five doses, a dose beginning in November and continuation for a total of five monthly doses will provide protection for most infants through April and is recommended for most areas of the United States. If prophylaxis is initiated in October, the fifth and final dose should be administered in February, which will provide protection for most infants through March. If prophylaxis is initiated in December, the fifth and final dose should be administered in April, which will provide protection for most infants through May.

Sporadic RSV infections occur throughout the year in most geographic locations. During times of low RSV prevalence (regardless of proportion of positive results), prophylaxis with palivizumab provides the least benefit because of the large number of children who must receive prophylaxis to prevent one RSV hospitalization.

Prophylaxis is not recommended for primary asthma prevention or to reduce subsequent episodes of wheezing.

Palivizumab prophylaxis is not recommended for prevention of health care-associated RSV disease.

References

American Academy of Pediatrics (AAP). Respiratory syncytial virus. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021-2024 Report of the Committee on Infectious Diseases. 32nd Ed. Elk Grove Village, IL: American Academy of Pediatrics; 2021: 628-636.

American Academy of Pediatrics (AAP). Respiratory syncytial virus. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012: 609-618.

American Academy of Pediatrics. Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Technical Report: Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):415-420.

American Hospital Formulary Service (AHFS). Drug Info. P​alivizumab (Synagis®). [Lexicomp Online Web site]. 02/26/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed July 27, 2021.

Berger J. Pulmonary hypertension in congenital heart disease. [Medscape Web site]. 02/13/2007. Available at: https://cme.medscape.com/viewarticle/551739 [via subscription only]. Accessed July 27, 2021.

Carbonell-Estrany X, Simoes EAF, Dagan R, et al. Motaizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Pediatrics. 2010;125(1):e35-e51.

Centers for Disease Control and Prevention (CDC). The National Respiratory and Enteric Virus Surveillance System (NREVSS). Respiratory syncytial virus (RSV) surveillance. [CDC Web site]. 07/17/2021. Available at: https://www.cdc.gov/surveillance/nrevss/rsv/index.html. Accessed July 27, 2021.

Centers for Disease Control and Prevention. Respiratory syncytial virus infection (RSV). Prophylaxis and High-Risk Groups. [CDC Web site]. 12/18/2021. Available at: https://www.cdc.gov/rsv/clinical/index.html. Accessed July 27, 2021.

Dunlap B, Weyer G. Pulmonary hypertension: diagnosis and treatment. Am Fam Physician. 2016;94(6):463-469.

Elsevier's Gold Standard. ClinicalKey. Palivizumab (Synagis®). [Clinical Key Web site]. 09/27/2018. Available at: https://www.clinicalkey.com/#!/  [via subscription only]. Accessed July 27, 2021. 

IBM Micromedex DrugDex®. Palivizumab (Synagis®). [IBM Micromedex® Web site]. 07/16/2020. Available at: https://www.micromedexsolutions.com/micromedex2/librarian/ssl/true [via subscription only]. Accessed July 27, 2021.
 
Lexi-Drugs. Palivizumab (Synagis®). [Lexicomp Online Web site]. 07/20/2021. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed July 27, 2021.
 
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.

Ralston SL, Lieberthal AS, Meissner HC, et al. American Academy of Pediatrics Clinical Practice Guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):1474-1502.
 
US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Synagis® (Palivizumab). [Prescribing Information]. [FDA Web site]. 05/12/2017.  Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed July 27, 2021.
 
US Food and Drug Administration (FDA). Department of Health and Human Services. Synagis® (Palivizumab). Product approval letter. [FDA Web site]. 03/21/2014. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/103770Orig1s5185ltr.pdf. Accessed July 27, 2021.  ​​

Coding

CPT Procedure Code Number(s)
90378

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)
S9562 Home 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

Revenue Code Number(s)
N/A



Coding and Billing Requirements


Policy History

9/13/2021
9/13/2021
08.00.22
Medical Policy Bulletin
Commercial
No