Blue Cross of Idaho Logo

Express Sign-on

Thank you for registering with Blue Cross of Idaho

If you are an Individual or Family Member under age 65, please register here.

If you are an Medicare or Medicare Supplement member, please register here.

New Options for Affordable Health Insurance

 

MP 5.01.10 Immune Prophylaxis for Respiratory Syncytial Virus

Medical Policy    
Section
Prescription Drug 
Original Policy Date
3/15/99
Last Review Status/Date
Reviewed with literature search/8:2013
Issue
8:2013
  Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


Description 

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infections in children. At highest risk are those younger than 2 years of age with prematurity, chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]), congenital heart disease, or multiple congenital anomalies. Immune prophylaxis against RSV is a prevention strategy to reduce the incidence of infection and its associated morbidity, including hospitalization, in high-risk infants.

Background

RSV infections typically occur in the winter months, starting from late October to mid-January and ending from March to May.(1) Considerable variation in the timing of community outbreaks is observed year to year. According to the Centers for Disease Control and Prevention (CDC), onset of the RSV season occurs when the median percentage of specimens testing positive for RSV is 10% higher over a 2-week period. During 1997-2006, an estimated 132,000 to 172,000 children aged younger than 5 years were hospitalized for RSV infection annually in the United States.(1)

Chronic lung disease (CLD, [formerly known as bronchopulmonary dysplasia]) is a general term for long-term respiratory problems in premature infants. CLD results from lung injury to newborns who, consequently, must use a mechanical ventilator and supplemental oxygen for breathing. With injury, the lung tissues become inflamed and scarring can result. Some of the causes of the lung injury include the following: prematurity, low amounts of surfactant, oxygen use, mechanical ventilation. Risk factors for developing CLD include: birth at less than 34 weeks’ gestation, birth weight less than 2,000 grams (4 pounds 6.5 ounces), hyaline membrane disease, pulmonary interstitial emphysema (PIE), patent ductus arteriosus (PDA), Caucasian, male infants, maternal womb infection (chorioamnionitis), and family history of asthma.

In contrast to the well-documented beneficial effect of breastfeeding against many viral illnesses, existing data are conflicting regarding the specific protective effect of breastfeeding against RSV infection. Breastfeeding should be encouraged for all infants in accordance with recommendations of the American Academy of Pediatrics. High-risk infants should be kept away from crowds and from situations in which exposure to infected people cannot be controlled. Participation in group child care should be restricted during the RSV season for high-risk infants whenever feasible. Parents should be instructed on the importance of careful hand hygiene. In addition, all high-risk infants 6 months of age and older and their contacts should receive influenza vaccine, as well as other recommended age-appropriate immunizations.

This policy does not address therapies to treat RSV infection.

Regulatory Status

In June 1998, the biologic Synagis® (palivizumab; MedImmune Inc, Gaithersburg, MD) was approved for marketing by the U.S. Food and Drug Administration (FDA) through the biologics licensing application for use in the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease. In July 2004, FDA approved a liquid formulation of Synagis®, supplied as a sterile solution ready for injection, thus providing improved convenience for administration. This formulation is used in the physician office or home setting.

RespiGam® RSV-IVIG for intravenous use was available from 1993 to 2009. It is no longer manufactured.

In August 2010, Motavizumab (proposed to be marketed as Rezield™, MedImmune Inc) received a complete response letter from FDA requesting additional clinical data on its biologics license application. Subsequently, AstraZeneca suspended Motavizumab development and upon the manufacturer’s request, FDA withdrew its biological license application.


Policy 

Monthly administration of immune prophylaxis for respiratory syncytial virus during the RSV season with palivizumab may be considered medically necessary in the following infants and children in accordance with current (2009) guidelines from the American Academy of Pediatrics:

1. Infants with chronic lung disease of prematurity (CLD, [formerly known as bronchopulmonary dysplasia]). Infants and children younger than 24 months of age who receive medical therapy (supplemental oxygen, bronchodilator, diuretic or chronic corticosteroid therapy) for chronic lung disease within 6 months before the start of the RSV season.

2. Infants born before 32 weeks’ gestation(31 weeks, 6 daysor less). Infants in this category may benefit from RSV prophylaxis, even if they do not have CLD. For these infants, major risk factors to consider include gestational age and chronologic age at the start of the RSV season. Infantsborn at 28 weeks of gestation or earlier (up to and including 28 weeks, 6 days) may benefit from prophylaxis during the RSV season, whenever that occurs during the first 12 months of life. Infants bornat 29 to 32 weeks of gestation may benefit most from prophylaxis if younger than 6 months of age at the start of the RSV season. In this setting, 32 weeks’ gestation refers to an infant born before the 32nd week of gestation (31 weeks, 6 days or less).

3. Infants born at 32 to less than 35 weeks’ gestation (defined as 32 weeks, 0 days through 34 weeks, 6 days). Infants younger than 3 months of age at the start of or born during RSV season, or who are likely to have an increased risk of exposure to RSV when at least one of the following risk factors is present:

  • Infant attends child care, defined as a home or facility where care is provided for any number of infants or young toddlers in the child care facility; or
  • Infant has a sibling younger than 5 years of age.

Infants in this gestational age category should receive prophylaxis only until they reach 3 months of age, maximum of 3 monthly doses.

4.Infants with congenital abnormalities of theairway or neuromusculardisease. Infants who have either congenital malformations of the airway or a neuromuscular condition that compromises handling of respiratory secretions.

5. Infantsand children with congenital heart disease. Children who are 24 months of age or younger with hemodynamically significant cyanotic or acyanotic congenital heart disease may benefit from palivizumab prophylaxis. Decisions regarding prophylaxis with palivizumab in children with congenital heart disease should be made on the basis of the degree of physiologic cardiovascular compromise. Children younger than 24 months of age with congenital heart disease who are most likely to benefit from immunoprophylaxis include:

  • Infants who are receiving medication to control heart failure;
  • Infants with moderate to severe pulmonary hypertension;
  • Infants with cyanotic heart disease.

After surgical procedures that use cardiopulmonary bypass, for children who still require prophylaxis, a postoperative dose of palivizumab may be considered medically necessary as soon as the patient is medically stable.

Immunoprophylaxis for respiratory syncytial virus is considered not medically necessary in:

  • 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 heart failure;
  • Infants with mild cardiomyopathy who are not receiving medical therapy for the condition.

Other indications for immune prophylaxis for respiratory syncytial virus are considered investigational including, but not limited to, immunocompromised children; patients with cystic fibrosis; or for use in controlling outbreaks of health care-associated disease.


Policy Guidelines 

Palivizumab is administered by intramuscular injection in a dose of 15 mg/kg of body weight per month. The anterolateral aspect of the thigh is the preferred injection site. Routine use of the gluteal muscle for the injection site can cause sciatic nerve damage.

Hospitalized infants who qualify for prophylaxis during the RSV season should receive the first dose of palivizumab 48 to 72 hours before discharge or promptly after discharge.

If an infant or child, who is receiving palivizumab immunoprophylaxis experiences a breakthrough RSV infection, they should continue monthly prophylaxis until a maximum of 5 doses for infants with congenital heart disease (CHD), CLD (formerly known as bronchopulmonary dysplasia), or preterm birth before 32 weeks’ gestation. This recommendation is based on the observation that high-risk infants may be hospitalized more than once in the same season with RSV lower respiratory tract disease and the fact that more than 1 RSV strain often co-circulates in a community.

Infants who qualify for prophylaxis in the 32 to 35 weeks' gestation age group should receive prophylaxis only until they reach 90 days of age or a maximum of 3 doses (whichever comes first).

RSV is known to be transmitted in the hospital setting and to cause serious disease in high-risk infants. 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 (eg, pediatric or neonatal intensive care unit or 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.

Palivizumab does not interfere with response to vaccines.

Palivizumab may interfere with RSV diagnostic tests that are immunologically-based (eg, some antigen detection-based assays).

Infants, especially high-risk infants, never should be exposed to tobacco smoke. In published studies, passive household exposure to tobacco smoke has not been associated with an increased risk of RSV hospitalization on a consistent basis. However, exposure to tobacco smoke is a known risk factor for many adverse health-related outcomes. Exposure to tobacco smoke can be controlled by the family of an infant at increased risk of RSV disease, and preventive measures will be less costly than palivizumab prophylaxis.

Initiation and Termination of Immunoprophylaxis

Initiation of immunoprophylaxis in November and continuation for a total of 5 monthly doses will provide protection into 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.

In the temperate climates of North America, peak RSV activity typically occurs between November and March, whereas in equatorial countries, RSV seasonality patterns vary and may occur throughout the year. The inevitability of the RSV season is predictable, but the severity of the season, the time of onset, the peak of activity, and the end of the season cannot be predicted precisely. Substantial variation in timing of community outbreaks of RSV disease from year to year exists in the same community and between communities in the same year, even in the same region. These variations occur within the overall pattern of RSV outbreaks, usually beginning in November or December, peaking in January or February, and ending by the end of March or sometime in April. Communities in the southern United States, particularly some communities in the state of Florida, tend to experience the earliest onset of RSV activity. In recent years, the national duration of the RSV season has been 21 weeks.(1)

Results from clinical trials indicate that palivizumab trough serum concentrations more than 30 days after the fifth dose will be well above the protective concentration for most infants. Five monthly doses of palivizumab will provide more than 20 weeks of protective serum antibody concentration. In the continental United States, a total of 5 monthly doses for infants and young children with congenital heart disease or chronic lung disease of prematurity or preterm birth before 32 weeks’ gestation (31 weeks, 6 days) will provide an optimal balance of benefit and cost, even with variation in season onset and end.

Data from CDC have identified variations in the onset and offset of the RSV season in the state of Florida that should affect the timing of palivizumab administration. Northwest Florida has an onset in mid-November, which is consistent with other areas of the United States. In north central and southwest Florida, the onset of RSV season typically is late September to early October. The RSV season in southeast Florida (Miami-Dade County) typically has its onset in July. Despite varied onsets, the RSV season is of equal duration in the different regions of Florida. Children who receive palivizumab prophylaxis for the entire RSV season should receive palivizumab only during the 5 months following the onset of RSV season in their region (maximum of 5 doses), which should provide coverage during the peak of the season, when prophylaxis is most effective.


Benefit Application
BlueCard/National Account Issues
 

State or national mandates (e.g., FEP) may dictate that all FDA-approved biologics may not be considered investigational and thus these biologics may be assessed on the basis of their medical necessity.


Rationale

This policy was originally created in 1999 and was regularly updated with searches of the MEDLINE database. The most recent literature search was performed for the period of July 2012 through June 18, 2013. The following is a summary of the key findings to date.

High-risk Infants

Systematic Reviews

In 2008, the Department of Public Health and Epidemiology, University of Birmingham, Birmingham, UK, released a health technology assessment (HTA) on immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children.(2) This HTA report was updated in 2011; the update developed the economic model from the first report by cost-effectiveness in different subgroups of children with RSV infection.(3) Thirteen studies published through August 2009 were included in this updated analysis. Most of the studies were small and not powered for the outcomes of interest, and the quality of reporting was also frequently poor. In the original HTA report, 2 randomized controlled trials (RCTs) (summarized below)(4,5) were used for establishing the relative risk of hospitalization in children given palivizumab compared with those without. No additional RCTs of palivizumab were found for the HTA update in 2011.(3)

Randomized Controlled Trials

Several RCTs have demonstrated the success of immune prophylaxis of RSV. In 2013, Blanken et al performed a multicenter, double-blind, randomized, placebo-controlled MAKI trial to investigate the potential causal role of RSV infection in the pathogenesis of wheezing illness during the first year of life, using palivizumab.(6) The trial randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Premature infants treated with palivizumab had a significant 61% relative decrease in the total number of wheezing days during the first year of life (95% confidence interval [CI], 56 to 65).(6) Moreover, the effect of RSV prevention on the number of wheezing days persisted in the postprophylaxis period (ie, starting at 2 months after the last injection) for a relative reduction of 73% (95% CI, 66 to 80). In addition, palivizumab treatment reduced hospitalizations related to RSV infection (12.6% in the RSV prevention group, as compared with 21.9% in the placebo group (p=0.04).(6)

In the 1998 Impact-RSV Study Group, prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission; 4.8% (48/1,002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group.(4) Similar reductions in other measures of RSV severity in breakthrough infections were also reported. In a 2003 double-blind, placebo-controlled randomized trial of 1287 children with hemodynamically significant CHD, Feltes et al reported prophylaxis with palivizumab was associated with a 45% reduction in hospitalization rate for RSV among children with congenital heart disease (CHD).(5) Hospitalization rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group. The authors concluded that prophylaxis with palivizumab is clinically effective for reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalization in high-risk children.

In 1997, the PREVENT Study Group reported on a trial that randomly assigned 510 infants with prematurity or CLD to receive either placebo or RSV-intravenous immunoglobulin (IVIg) infusions monthly for 5 months. The authors reported a 41% reduction in hospitalization due to RSV infection and reductions in other measures of severity of RSV infection when it did occur.(7) Palivizumab eventually became the preferred product over the IVIg product due to the convenience of intramuscular administration, safety concerns regarding immunoglobulin pooled from multiple donors, and the unlimited supply of a bioengineered product.

In 1998, the American Academy of Pediatrics (AAP) published revised guidelines regarding the use of RSV-IVIg or palivizumab for RSV immune prophylaxis, which focused on infants with CLD and preterm infants.(8) In 2003, the AAP Red Book, which summarizes immunization recommendations and the AAP policy statement on the prevention of RSV added indications for children with hemodynamically significant heart disease.(9)

Immune prophylaxis has also been suggested for patients 24 months of age or younger with congenital heart disease (CHD). AAP guidelines indicate the use of palivizumab in children with CHD should be based on the degree of cardiovascular compromise. Infants with CHD who are younger than 12 months may benefit from palivizumab if they are receiving medication for heart failure, have moderate-to-severe pulmonary hypertension, or have cyanotic heart disease.

The 2003 recommendation by AAP(8) was based on the results of the Feltes RCT noted above.(5) In 2009, AAP updated its guidelines regarding the use of immune prophylaxis for RSV. The new AAP Red Book 2012 chapter on RSV was reviewed and no substantive changes noted.(10) The following is a summary, provided by the AAP, of the major changes that were made to the 2009 guidelines:

“1. Recommendations for initiation and termination of prophylaxis are modified to reflect current CDC descriptions of RSV seasonality in different geographic locations within the United States.

2. The recommendations remain unchanged for infants with congenital heart disease, chronic lung disease of prematurity and birth before 32 weeks' gestation.

3. Regardless of the month when the first dose is administered, the recommendation for a maximum number of 5 doses for all geographic areas is emphasized for infants with hemodynamically significant congenital heart disease, chronic lung disease of prematurity or birth before 32 weeks' gestation and for a maximum number of 3 doses for infants with a gestational age of 32 to 35 weeks without hemodynamically significant congenital heart disease or chronic lung disease.

4. Risk factors for severe RSV lower respiratory tract disease among infants born between 32 to 35 weeks' gestation have been modified to include only:

a. Infant attends child care

b. Siblings living in the household are less than 5 years of age

5. Infants 32 to 35 weeks' gestation age who are born within the 3 months before the onset of RSV season and throughout the RSV season will qualify for prophylaxis if they have at least one [of the modified] risk factors. Earlier recommendations required 2 of 5 [different] risk factors.

6. Infants who qualify for prophylaxis in the 32 to 35 weeks' gestation age group should receive prophylaxis only until they reach 90 days of age or a maximum of 3 doses (whichever comes first). This is a change from the previous recommendation for 5 months of prophylaxis.

7. The AAP's definition of gestational age is used throughout this document. For example, 32 to 35 weeks' gestation is defined as 32 weeks, 0 days through 34 weeks, 6 days.”

In August 2009, AAP released a policy statement (including references and evidence grading) that supported their revised indications for the use of palivizumab for the prevention of respiratory syncytial virus infections.(11) In commenting on their 2009 recommendations, the AAP policy statement indicates, "they [the 2009 AAP recommendations] specifically target infants in this [32 to less than 35 weeks' gestational age] with consistently identified risk factors for RSV hospitalization during the period of greatest risk, which is the first 3 months of life.”

In 2008, Cohen et al evaluated the characteristics of patients (n=19,548) enrolled in The Palivizumab Outcomes Registry with CHD over the 4 RSV seasons.(12) The Palivizumab Outcomes Registry prospectively collected data on patients who received RSV prophylaxis with palivizumab during the 2000-2004 RSV seasons. The percentage of registry subjects with CHD increased from 4.8% (102/2,116) in the first season to 11.4% (688/6,050) in the last season. Across all 4 seasons, 1500 subjects with CHD were enrolled; 71% of whom had acyanotic CHD. The proportion with cyanotic CHD increased from 19.6% (20/102) in the 2000-2001 season to 37.5% (258/688) in the 2003-2004 season, while the proportion of all CHD in the registry more than doubled during this time. The cumulative RSV hospitalization rate was 1.9% among patients with CHD who received prophylaxis. Among subjects with cyanotic and acyanotic CHD, hospitalization rates were 2.6% and 1.6%, respectively. The authors concluded, “…the prospective data collected in the Palivizumab Outcomes Registry provides the largest published dataset available on infants with CHD receiving palivizumab; shows low hospitalization rates, use consistent with prelicensure clinical trial data and the revised American Academy of Pediatrics guidelines.”

A review article discussed the development of a second-generation humanized monoclonal antibody (mAb), motavizumab, which is no longer under study in Phase III clinical trials, and most recently, a third generation mAb, Numax-YTE.(13)

Cystic Fibrosis

A Cochrane review was published in 2010 and updated in 2013, assessing the use of palivizumab in children with cystic fibrosis.(14,15) Based on a literature search through October 2012, 1 randomized comparative trial met the inclusion criteria of both reviews. In the study, 186 infants younger than 2 years with cystic fibrosis were randomly assigned to receive 5 monthly doses of palivizumab (n=92) or placebo (n=94). One member of each group was hospitalized for RSV within the 6-month follow-up period. The rate of adverse event noted in each group was relatively high, with serious adverse events not significantly different between the palivizumab and placebo groups (20.2% and 17.3%, respectively). The authors noted that it was not possible to draw conclusions on the tolerability and safety of RSV immune prophylaxis in cystic fibrosis. The single study reported similar adverse events but did not specify how adverse events were classified. No clinically meaningful outcome differences were noted at 6-month follow-up. The authors of the review called for additional randomized studies to establish both efficacy and safety of immune prophylaxis in children with cystic fibrosis.

Immunodeficiencies

The use of RSV-IVIg or palivizumab in patients with documented immunodeficiencies has also been suggested. The AAP guidelines note, "Palivizumab or RSV-IVIg has not been evaluated in randomized trials in immunocompromised children. Although specific recommendations for immunocompromised patients cannot be made, children with severe immunodeficiencies (eg, severe combined immunodeficiency or severe acquired immunodeficiency syndrome) may benefit from prophylaxis. If these infants and children are receiving standard immune globulin intravenous monthly, physicians may consider substituting RSV-IVIg during the RSV season."

Immunocompromised patients undergoing stem-cell transplantation are also at risk for potentially lethal respiratory viral infections. Cortez et al studied whether RSV-IVIg provided sufficient RSV immune prophylaxis to prevent RSV pneumonia in 54 patients undergoing stem-cell transplantation.(16) The authors reported a low incidence of RSV infection in the 54 RSV-IVIg patients, as well as in 31 patients not enrolled in the study, and could not determine the preventive effect of RSV-IVIg. In a literature review, Hynicka and Ensor found data are limited on RSV prophylaxis in immunocompromised adult patients.(17) The only prospective study identified in the review was by Kassis et al(18) in which intravenous pavilizumab was given to 16 high-risk stem-cell transplant patients to prevent the nosocomial spread of RSV infection from 5 stem-cell transplant patients. After 1 week, no further RSV cases occurred, but whether controlling the spread of RSV on the stem-cell transplant unit was related to RSV prophylaxis versus implementation of strict quarantine and infection control practices cannot be determined.

Duration of Prophylaxis

The RSV season typically occurs from November to April. Within the United States, the inevitability of the RSV season is predicable, but the severity of the season and time of onset are variable from year to year and also between geographic areas within a given year. This has led to requests for either earlier or later immunoprophylaxis, or greater than 5 monthly doses. Nevertheless, as pointed out by Meissner et al from the Centers of Disease Control and Prevention (CDC), “…this yearly and regional variation still occurs within the overall pattern of RSV outbreaks, usually beginning in November or December, peaking in January or February, and ending by March. Communities in the southern region tend to experience the earliest onset of RSV activity, and Midwestern states tend to experience the latest onset, but community to community variation in timing precludes using either national or regional data to precisely predict individual community RSV outbreaks. The duration of the season for western and northeast regions typically occurs between that noted in the South and the Midwest.” The authors point out that the recommendation for 5 monthly doses is derived from the randomized studies of palivizumab. A serum palivizumab concentration of greater than 30 μg/mL is the target level for protection, and in randomized studies, the trough level of palivizumab exceeded 30 μg/mL for at least 30 days after the fifth dose. This indicates that 5 monthly doses will provide substantially more than 20 weeks of protective serum antibody levels, covering most of the RSV season even with variation in season onset and end.(19)

Compliance

Frogel et al reviewed the medical literature on compliance with palivizumab therapy and the relation between hospitalization rates in fully compliant and less compliant groups.(20) A total of 25 articles and abstracts met review inclusion criteria. Significant heterogeneity was detected due to between-study differences in the population studied and the definition of compliance used. Differences in compliance definitions led to a compliance rate range of 25% to as high as 100%, compared to rates in licensing studies of 92% and 93%. This led the authors to the conclusion that compliance in practice is far more variable. Minorities and patients on Medicaid were less likely to receive the full complement of palivizumab doses, while patients participating in a home health program tended to have higher compliance and less hospitalization. Home health programs were defined as nurse-delivered injections performed in the home setting.

Ongoing Clinical Trials

A search of online site ClinicalTrials.gov in August 2012 identified 2 active observational studies addressing palivizumab in infants 2 years or younger (NCT01155193, NCT01269528).

Clinical Input Received through Physician Specialty Societies and Academic Medical Centers

In response to requests, input was received through 3 physician specialty societies (7 responders) while this policy was under review in 2009. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. Almost all of those providing input agreed with the policy statements approved in October 2009; these statements are in agreement with the 2009 AAP guidelines.

Summary

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory infections in children. At highest risk are those younger than 2 years of age with prematurity, chronic lung disease (formerly known as bronchopulmonary dysplasia), congenital heart disease, or multiple congenital anomalies. Immune prophylaxis against RSV is a prevention strategy to reduce the incidence of infection and its associated morbidity, including hospitalization, in high-risk infants.

Based on the weight of the clinical evidence from randomized clinical trials, systematic reviews and strong clinical consensus, immune prophylaxis for RSV has demonstrated reductions in RSV-related hospitalizations in select populations of susceptible infants and children. Therefore, immune prophylaxis for RSV may be considered medically necessary for the patients listed in the policy statement above. For all other uses of immune prophylaxis, the clinical evidence is not convincing that RSV hospitalizations will decrease. Therefore, the policy statements above note indications which are considered investigational or not medically necessary. The policy statements are in agreement with the 2009 American Academy of Pediatrics Guidelines.

Practice Guidelines and Position Statements

In 2003, the AAP released a policy statement with revised indications for the use of palivizumab and RSV-IVIg for the prevention of RSV infections.(9)

In June 2009, the AAP released updated guidelines regarding the use of immune prophylaxis for RSV. The updated guidelines were published in the new AAP Red Book 2012 in the chapter on RSV.(10)

In August 2009, the AAP released a policy statement (including references and evidence grading) with revised indications for the use of palivizumab for the prevention of RSV infections.(11)

Medicare National Coverage

There is no national coverage determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of local Medicare carriers.

References:

 

 

 

 
  1. Respiratory syncytial virus--United States, July 2011-January 2013. MMWR Morb Mortal Wkly Rep 2013; 62(8):141-44.
  2. 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.
  3. Wang D, Bayliss S, C. M. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses. Health Technol Assess. 2011; 15(5):i-xii, 1-123.
  4. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102(3 Pt 1):531-7.
  5. Feltes TF, Cabalka 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):532-40.
  6. Blanken MO, Rovers MM, Molenaar JM et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013; 368(19):1791-9.
  7. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. The PREVENT Study Group. Pediatrics 1997; 99(1):93-9.
  8. Prevention of respiratory syncytial virus infections: indications for the use of palivizumab and update on the use of RSV-IGIV. American Academy of Pediatrics Committee on Infectious Diseases and Committee of Fetus and Newborn. Pediatrics 1998; 102(5):1211-6.
  9. Meissner HC, Long SS. 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 Pt 1):1447-52.
  10. Torres VE, Chapman AB, Devuyst O et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012; 367(25):2407-18.
  11. From the American Academy of Pediatrics: Policy statements--Modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics 2009; 124(6):1694-701.
  12. Cohen SA, Zanni R, Cohen A et al. Palivizumab use in subjects with congenital heart disease: results from the 2000-2004 Palivizumab Outcomes Registry. Pediatr Cardiol 2008; 29(2):382-7.
  13. Wu H, Pfarr DS, Losonsky GA et al. Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol 2008; 317:103-23.
  14. Robinson KA, Odelola OA, Saldanha I et al. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis. Cochrane Database Syst Rev 2010; 2:CD007743.
  15. Robinson KA, Odelola OA, Saldanha IJ et al. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis. Cochrane Database Syst Rev 2013; (6):CD007743.
  16. 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):834-8.
  17. Hynicka LM, Ensor CR. Prophylaxis and treatment of respiratory syncytial virus in adult immunocompromised patients. Ann Pharmacother 2012; 46(4):558-66.
  18. Kassis C, Champlin RE, Hachem RY et al. Detection and control of a nosocomial respiratory syncytial virus outbreak in a stem cell transplantation unit: the role of palivizumab. Biol Blood Marrow Transplant 2010; 16(9):1265-71.
  19. Meissner HC, Anderson LJ, Pickering LK. Annual variation in respiratory syncytial virus season and decisions regarding immunoprophylaxis with palivizumab. Pediatrics 2004; 114(4):1082-4.
  20. Frogel MP, Stewart DL, Hoopes M et al. A systematic review of compliance with palivizumab administration for RSV immunoprophylaxis. J Manag Care Pharm 2010; 16(1):46-58.  
Codes Number Description
CPT   90378                               Respiratory syncytial virus immune globulin for intramuscular use, 50 mg, each
   96365 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
   96366 Each additional hour (list separately in addition to code for primary procedure)
  96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
ICD-9 Procedure 99.29 Injection or infusion of other therapeutic or prophylactic substance
ICD-9 Diagnosis 396 Diseases of mitral and aortic valves (code range)
   417 Other disease of pulmonary circulation (code range)
   424 Other diseases of endocardium (code range)
   425 Cardiomyopathy (code range)
   428 Heart failure (code range)
  491 Chronic bronchitis (code range)
  745 Bulbus cordis anomalies and anomalies of cardiac septal closure (code range)
   746 Other congenital anomalies of the heart (code range)
   747 other congenital anomalies of the circulatory system (code range)
   765.2 Weeks of gestation (5th digit indicates specific weeks of gestation)
   V07.2 Prophylactic immunotherapy
   V46.2 Supplemental oxygen
HCPCS J1565 Injection, respiratory syncytial virus immune globulin, intravenous, 50mg (i.e., RespiGam)
ICD-10-CM (effective 10/1/14) I08.0 – I08.9 Multiple valve diseases code range  
   I28.0 – I28.9 Other diseases of pulmonary vessels code range  
   I34.0 – I34.9 Nonrheumatic mitral valve disorders code range  
   I35.0 – I35.9 Nonrheumatic aortic valve disorders code range  
   I36.0 – I36.9 Nonrheumatic tricuspid valve disorders code range  
   I37.0 – I37.9 Nonrheumatic pulmonary valve disorders code range  
   I42.0 – I42.9 Cardiomyopathy code range  
   I43 Cardiomyopathy in diseases classified elsewhere  
   I50.1 – I50.9 Heart failure code range  
   J41.0 – J42  Chronic bronchitis code range  
   J44.0 – J44.9 Other chronic obstructive pulmonary disease code range  
   P07.00-P07.32 Disorders of newborn related to short gestation and low birth weight, not elsewhere classified code range  
  P27.0-P27.9 Chronic respiratory disease originating in the perinatal period (includes bronchopulmonary dysplasia P27.1)  
  P28.0 – P28.9 Other respiratory conditions originating in the perinatal period code range  
  Q20.0 – Q28.9 Congenital malformations of the circulatory system code range  
ICD-10-PCS (effective 10/1/14)    ICD-10-PCS codes are only used for inpatient services.  
  3E0234Z   Administration, physiological systems and anatomical regions, introduction, muscle, percutaneous, serum, toxoid and vaccine  
    3E0334Z Administration, physiological systems and anatomical regions, introduction, peripheral vein, percutaneous, serum, toxoid and vaccine 
Type of Service Prescription Drug  
Place of Service Outpatient  


Index
Palivizumab
RespiGam
Respiratory Syncytial Virus
RSV-IVIg
Synagis

Policy History 

Date Action Reason
03/15/99 Add to Prescription Drug Section New policy
11/10/99 Replace policy New CPT code; policy unchanged
02/15/02 Replace policy Policy updated with new references; policy statement unchanged
10/09/03 Replace policy Policy revised; added indication for palivizumab for infants with hemodynamically significant heart disease and for those born between 32 and 35 weeks’ gestation with additional high risk factors. Policy based on AAP guidelines.
11/09/04 Replace policy Literature review update for the period between June 2003 and September 2004; references added. RSV immune prophylaxis in stem-cell transplantation added to the investigational policy statement.
09/27/05 Replace policy Policy updated with literature review; no change in policy statement. Information added regarding new liquid formulation of Synagis to Policy Guidelines section. Reference 9 added, discussing length and variation of RSV season.
12/14/05 Replace policy-coding update only CPT coding updated
09/18/07 Replace policy Policy updated with literature search through July 2007; treatment is considered investigational for children over 2 years of age. No changes in policy statements. Reference numbers 10–12 added.
12/13/07 Replace policy-correction only Language “treatment…over 2 years of age” added to 9/18/07 policy history.
10/06/09 Replace policy Policy updated with literature search from August 2007 through August 2009; clinical input reviewed; The policy statement has been modified to reflect the 2009 AAP; new reference numbers 13-17 added.
10/08/10 replace policy Policy updated with literature search. References 15 and 16 added. Policy statements unchanged.
10/04/11 Replace policy Policy updated with literature search. Policy statement number 4 modified with removal of “born before 35 weeks of gestation” to be consistent with the AAP guidelines. Deleted “congestive” from “congestive heart failure” in policy statements. Other policy statements are unchanged.
9/13/12 Replace policy Policy updated with literature search. Rationale reorganized. References 1, 13 and 15-16 added. Policy statements unchanged.
8/8/13 Replace policy Policy updated with literature search through June 18, 2013. References 3 and 6 added; references 1, 10, and 15 updated. Policy statements unchanged.
2/13/14 Replace policy - correction only Removed contradictory statement in the Rationale section about RSV-IVIg being contraindicated in children with cyanotic CHD.