Aetna considers standard, heptavalent pneumococcal conjugate, and pneumococcal 13-valent conjugate vaccines medically necessary according to the recommendations of the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP).

Standard Pneumococcal Vaccine:

Aetna considers standard 23-valent pneumococcal polysaccharide vaccine (PPV23, e.g., Pneumovax, Pnu-immune) medically necessary for all individuals aged 65 years or older.

Aetna considers standard pneumococcal vaccine medically necessary for persons over 2 years of age with any of the following conditions:

1. Acquired or congenital immunodeficiency (including HIV infection) 
2. Adults aged 19 through 64 years who have asthma
3. Adults aged 19 through 64 years who smoke cigarettes
4. After heptavalent pneumococcal conjugate vaccine (PCV7) in Alaska Native or American Indian children aged 24 through 59 months who are living in areas where the risk of invasive pneumococcal disease is increased
5. Alaska Native and American Indian persons aged 50 to 64 years who are living in areas where the risk of invasive pneumococcal disease is increased, when recommended by public health authorities
6. Alcoholism (adults)
7. Asplenia (functional or anatomic)
8. Cerebrospinal fluid leaks
9. Chronic cardiovascular disease
10. Chronic liver disease (including cirrhosis)
11. Chronic pulmonary disease
12. Chronic renal failure or nephrotic syndrome
13. Diabetes mellitus
14. Metastatic or hematologic malignancies
15. Multiple myeloma (adults)
16. Other conditions associated with immunosuppression (such as organ transplantation, bone marrow transplantation, and persons on immunosuppressive chemotherapy (including corticosteroids))
17. Persons living in special environments or social settings with an identified increased risk of pneumococcal disease 
18. Persons who have or are planning to receive a cochlear implant (see CPB 0013 - Cochlear Implants and Auditory Brainstem Implants)
19. Sickle cell disease.

Aetna considers standard pneumococcal vaccine experimental and investigational for other indications because its effectiveness for indications other than the ones listed above has not been established.

Routine re-vaccination is not recommended by the CDC.  In accordance with the CDC’s recommendations, Aetna considers re-vaccination medically necessary only for the following groups:

• Persons aged 65 years or older if they received vaccine 5 or more years previously and was less than 65 years of age at the time of vaccination
• Persons aged 2 to 64 years with asplenia.  If member is more than 10 years of age, a single re-vaccination is considered medically necessary 5 or more years after previous dose; if member is 10 years of age or younger, re-vaccination is considered medically necessary 3 years after previous dose
• Persons 2 years of age or older who are immunocompromised, have sickle cell disease, or functional or anatomic asplenia.  A single re-vaccination is considered medically necessary if 5 or more years have elapsed since receipt of the first dose; if the member is 10 years of age or younger, re-vaccination is considered medically necessary 3 years after previous dose.

In addition, re-vaccination with the 23-valent pneumococcal polysaccharide vaccine is considered medically necessary for high-risk individuals who received the 14-valent polysaccharide vaccine, which was in use prior to 1983.

Re-vaccination has no proven value for other groups.

Heptavalent Pneumococcal Conjugate Vaccine:

According to the recommendations of the CDC’s Advisory Committee on Immunization Practices, Aetna considers heptavalent pneumococcal conjugate vaccine (PCV7, e.g., Prevnar, Prevenar) medically necessary for all children under 2 years of age, and high-risk children between the ages of 2 and 5 years.  High-risk groups include children with:

• Immunocompromising conditions, including (i) congenital immunodeficiencies, B- (humoral) or T-lymphocyte deficiency; complement deficiencies, particularly c1, c2, c3, and c4 deficiency; and phagocytic disorders, excluding chronic granulomatous disease, (ii) diseases associated with immunosuppressive therapy or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkin’s disease; or solid organ transplantation, and (iii) renal failure and nephrotic syndrome
• Infection with human immunodeficiency virus
• Sickle-cell disease and other sickle cell hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction
• Chronic illnesses, including
   
  
  • Cerebrospinal fluid leaks
  • Children who have or are planning to receive a cochlear implant (see CPB 0013 - Cochlear Implants and Auditory Brainstem Implants)
  • Chronic cardiac disease, particularly cyanotic congenital heart disease and cardiac failure
  • Chronic pulmonary disease, excluding asthma unless on high dose corticosteroid therapy
  • Diabetes mellitus.

Based on the ACIP’s recommendations, Aetna considers heptavalent pneumococcal conjugate vaccination medically necessary for all other children aged 24 to 59 months, including the following populations identified by ACIP as a priority:

• Children aged 24 to 35 months
• Children of African-American descent
• Children of Alaska Native or American Indian descent
• Children who attend group day care centers (defined as a setting outside the home where a child regularly spends over 4 hours/week with more than 2 unrelated children under adult supervision).

Aetna considers heptavalent pneumococcal conjugate vaccine experimental and investigational for other groups because its effectiveness for groups other than the ones listed above has not been established.

Pneumococcal 13-valent Conjugate Vaccine (PCV13, Prevnar 13)

According to the recommendations of the CDC’s Advisory Committee on Immunization Practices, Aetna considers pneumococcal 13-valent conjugate vaccine (PCV13, Prevnar 13) medically necessary for all children aged 2 through 59 months, and high-risk children aged 5 through 18 years.  High-risk groups include children with:

• Chronic illnesses, including:
   
  
  • Cerebrospinal fluid leaks
  • Children who have or are planning to receive a cochlear implant (see CPB 013 - Cochlear Implants and Auditory Brainstem Implants)
  • Chronic cardiac disease, particularly cyanotic congenital heart disease and cardiac failure
  • Chronic pulmonary disease, excluding asthma unless on high dose corticosteroid therapy
  • Diabetes mellitus
     
• Immunocompromising conditions, including (i) congenital immunodeficiencies, B-(humoral) or T-lymphocyte deficiency; complement deficiencies, particularly c1, c2, c3, and c4 deficiency; and phagocytic disorders, excluding chronic granulomatous disease, (ii) diseases associated with immunosuppressive therapy or radiation therapy, including malignant neoplasms, leukemias, lymphomas, and Hodgkin’s disease; or solid organ transplantation, and (iii) renal failure and nephrotic syndrome
• Infection with human immunodeficiency virus
• Sickle-cell disease and other sickle cell hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction.

Aetna considers routine use of 13-valent pneumococcal conjugate vaccine (PCV 13; Prevnar 13) medically necessary for adults aged 19 years or older with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants.

Aetna considers heptavalent pneumococcal 13-valent conjugate vaccine experimental and investigational for other groups because its effectiveness for groups other than the ones listed above has not been established.

This policy is based on the recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (CDC/ACIP), the U.S. Preventive Services Task Force (USPSTF), the American Academy of Pediatrics (AAP) Committee on Infectious Diseases, the American College of Physicians Task Force on Adult Immunization, and the Infectious Diseases Society of America.

Pneumococcal disease is an infection with the bacteria Streptococcus pneumoniae, which causes pneumonia, bacteremia, and meningitis.  Pneumococcal disease is a significant cause of morbidity and mortality in the United States.  Population-based surveillance studies have reported annual invasive pneumococcal disease rates of at least 15 to 19/100,000 population and pneumococcal meningitis rates of 0.3 to 1.2/100,000.  Significantly higher incidence rates are reported for persons less than 5 years of age or over age 65; African Americans, Native Americans, and Alaska Natives; nursing home residents; alcoholics; and those with chronic medical or immunodeficient conditions.

Pneumococcal disease accounts for about 15 % of severe community-acquired pneumonia, which has a case-fatality rate (proportion of cases resulting in death) of 9 to 26 %.  Pneumococcal bacteremia and meningitis are also associated with high case-fatality rates.  The highest case-fatality rates from invasive pneumococcal infection occur in elderly persons (30 to 43 %) and patients with co-morbid conditions (25 to 27 %).

Standard pneumococcal vaccine:

Standard (unconjugated) pneumococcal polysaccharide vaccine (Pneumovax, Pnu-Immune) contains 23 purified capsular polysaccharide antigens of S. pneumoniae, and is protective against 88 % of the strains of S. pneumoniae causing bacteremic pneumococcal disease reported in the United States.  The 6 serotypes that most frequently cause invasive drug-resistant pneumococcal infection in the United States are represented in the 23-valent vaccine.  These vaccines were licensed in the United States in 1983 and replaced an earlier 14-valent formulation that was licensed in 1977.

Clinical studies have demonstrated the effectiveness of standard pneumococcal vaccine in reducing the incidence of pneumococcal pneumonia in the elderly and in immunocompetent high-risk groups.  A meta-analysis combining the most recent trials reported that vaccinated individuals had 11 fewer episodes of definitive pneumococcal pneumonia and 25 fewer episodes of presumptive pneumococcal pneumonia per 1,000 subjects (Fine, 1994).  Case-control studies and indirect cohort studies support the protective value of vaccine in immunocompetent recipients, with vaccine efficacy estimates of 60 to 75 % reported, but not in severely or relatively immunocompromised individuals, including those with alcoholism, chronic renal failure, immunoglobulin deficiency, nephrotic syndrome, sickle cell disease, multiple myeloma, metastatic or hematologic malignancies, or systemic lupus erythematosus.  For some of these disorders, efficacy point estimates suggest a benefit but the confidence intervals are wide and include the possibility of no benefit.

The U.S. Preventive Services Task Force concluded that there is insufficient evidence to recommend for or against pneumococcal vaccine as an efficacious vaccine for immunocompromised individuals, but noted that recommendations for vaccinating these persons may be made on other grounds, including high incidence and case-fatality rates of pneumococcal disease and minimal adverse effects from vaccine.

Immunocompromised conditions associated with high risk for pneumococcal disease include alcoholism, cirrhosis, chronic renal failure, nephrotic syndrome, sickle cell disease, multiple myeloma, metastatic or hematologic malignancies, acquired or congenital immunodeficiencies (including HIV infection), and other conditions associated with immunosuppression, such as organ transplant.

For most individuals, accepted guidelines suggest a single vaccination is sufficient.  The CDC and UPSPTF do not recommend routine revaccination, but state that it may be appropriate to consider revaccination in certain immunocompetent individuals at highest risk for morbidity and mortality from pneumococcal disease who were vaccinated more than 5 years previously.  These authorities also state that it may be appropriate to consider periodic re-vaccination of certain high-risk immunocompromised patients, who are likely to have poor initial antibody response and rapid decline of antibodies after vaccination.  In addition, re-vaccination with the 23-valent pneumococcal polysaccharide vaccine may be appropriate for high-risk individuals who received the 14-valent polysaccharide vaccine, which was in use prior to 1983.

Standard pneumococcal vaccine may be given with other vaccines.  No data indicate that administration of pneumococcal vaccine with DTP, poliovirus, influenza, or other vaccines increases the severity of reactions or diminishes the responses.

Standard pneumococcal vaccine is not indicated in the prophylaxis of otitis media in children.  The safety of pneumococcal vaccine in pregnancy has not been evaluated.

There is insufficient evidence that pneumococcal vaccine effects the course of bronchiectasis.  In a Cochrane review, Chang and colleagues (2007) assessed the effectiveness of pneumococcal vaccine as routine management in children and adults with bronchiectasis in reducing the severity and frequency of respiratory exacerbations and pulmonary decline.  The authors concluded that currently there is a lack of reliable evidence to support or refute the routine use of pneumococcal vaccine as routine management in children and adults with bronchiectasis.  Randomized controlled studies examining the effectiveness of this intervention using various vaccine types in different age groups are needed.

Heptavalent pneumococcal conjugate vaccine:

A 7-valent pneumococcal conjugate vaccine (Prevnar^TM, Prevenar^TM ) has been introduced by Wyeth Lederle for use in children.  The FDA has approved of this protein-polysaccharide conjugate vaccine for prevention of invasive pneumococcal disease (meningitis and bacteremia) in infants and toddlers.

The American Academy of Pediatrics and the CDC's ACIP recommended pneumococcal polyvalent vaccine for routine use in all children 2 and under, and for black, Alaskan Native, and Native American toddlers up to age 5, as well as for those with sickle-cell anemia, HIV infection, or other immunodeficiency diseases.  For infants, the AAP and ACIP recommends that the vaccine be given in 4 doses at 2, 4, 6, and 12 to 15 months; for children who are 7 to 11 months, 3 doses; for children who are 12 to 23 months, 2 doses; and for children 2 years or older, only 1 dose is needed.  See table below.

Table: Numbers of doses of Prevnar recommended by the ACIP for average risk children in each age range:

Pneumococcus is the most frequent cause of otitis media, pneumonia, and bacteremia in children, as well as the principle cause of childhood bacterial meningitis.  The most susceptible to pneumococcal diseases are children less than 2 years old.  Standard pneumococcal polysaccharide vaccines are poorly immunogenic in this age group.  The new protein-polysaccharide conjugate vaccine is immunogenic during infancy and is capable of providing long-term immunity.

Pneumococcal conjugate vaccine targets the seven serotypes (strains) of Streptococcus pneumonia that are responsible for 85 % of bacterial pneumonia in children.  The serotypes contained in the vaccine are also commonly associated with antibiotic resistance.

There is reliable evidence of the effectiveness of pneumococcal conjugate vaccine.  A 3-year, multi-center clinical trial involving 37,868 children reported that the pneumococcal conjugate vaccine was effective against invasive pneumococcal disease caused by seven prevalent serotypes of bacteria.  Pneumococcal conjugate vaccine had an efficacy rate of 97 % against invasive pneumococcal disease with vaccine serotypes, and a 93 % efficacy rate for disease with any serotype.  Children who received the pneumococcal vaccine were 1/3 less likely to develop x-ray confirmed pneumonia compared to children who received a conjugate meningococcal vaccine as a control.  Children who received the vaccine were 73 % less likely to have had severe pneumonia, and 89 % less likely to develop pneumococcal meningitis and bacteremia.  The results also suggested efficacy against frequent, recurrent otitis media; vaccinated children were 20 % less likely to have otitis media severe enough to require drainage tubes.

Although preliminary evidence indicates that pneumococcal conjugate vaccine may be safely administered with other childhood vaccines, the ACIP has recommended that further studies be performed on the safety of vaccine co-administration.

The FDA cautions that the pneumococcal conjugate vaccine is not indicated for use in adults.

A phase III trial evaluating the efficacy of the pneumococcal conjugate vaccine against pneumococcal otitis media is ongoing in Finland.  Wyeth Lederle is planning a supplemental filing for the otitis media indication.

The ACIP recommends pneumococcal vaccination for persons who have or are scheduled to receive a cochlear implant.  The ACIP recommends that children with cochlear implants aged less than 24 months should receive 7-valent pneumococcal conjugate vaccine, as is universally recommended; children with a lapse in vaccination should be vaccinated according to the catch-up schedule.  The ACIP recommends that children aged 24 to 59 months with cochlear implants who have not received pneumococcal conjugate vaccine should be vaccinated according to the high-risk schedule; children with a lapse in vaccination should be vaccinated according to the catch-up schedule for persons at high risk.  Children who have completed the 7- valent pneumococcal conjugate vaccine series should receive standard 23-valent pneumococcal vaccine more than 2 months after vaccination with 7- valent pneumococcal vaccine.  Persons aged 5 to 64 years with cochlear implants should receive standard 23-valent pneumococcal vaccine according to the schedule used for persons with chronic illnesses; a single dose is indicated.  The ACIP advises that persons planning to receive a cochlear implant should be up-to-date on age-appropriate pneumococcal vaccination more than 2 weeks before surgery, if possible.

Pneumococcal 13-valent Conjugate Vaccine (PCV13, Prevnar 13)

The CDC's ACIP voted on February 24, 2010 to recommend the use of a 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13) (Wyeth Pharmaceuticals Inc.), which provides broader protection for young children against pneumococcal diseases.  The vote came after the FDA had approved the vaccine for active immunization of infants and children aged 6 weeks through 5 years (prior to the 6th birthday) against Streptococcus pneumonia, which causes invasive pneumococcal diseases, such as pneumonia and meningitis, and against otitis media.  The new version of the vaccine protects against 6 more serotypes of Streptococcus pneumonia than the original version and is intended to replace PCV7.  Unlike PCV7, PCV13 includes serotype 19A, which is the most common serotype causing invasive pneumococcal infections in children.  In addition to serotype 19A, PCV13 also contains conjugated antigens representing serotypes 1, 3, 4, 5, 6A and B, 7F, 9V, 14, 18C, 19F, and 23F.

The FDA approval on February 24, 2010 was based on data from a clinical trial program including 13 core Phase 3 studies involving more than 7,000 infants and young children that showed the new 13-valent vaccine elicited immune responses comparable to that achieved with the 7-valent PCV.  FDA 2010 product information identified a 4-dose infant/toddler schedule to be administered at ages 2 months, 4 months, 6 months, and 12 to 15 months.

Adverse events were similar for both vaccines and most commonly included injection site reactions (pain, erythema, and inflammation), as well as irritability, decreased appetite, and fever.

The CDC's ACIP approved the following recommendations:

• Un-vaccinated infants and children: PCV13 is recommended for all children aged 2 through 59 months.  In the United States, infants receive a "3 plus 1" dosing schedule, with doses at 2, 4, and 6 months and a booster dose at 12 to 15 months.  Older children will follow the schedule currently recommended for PCV7.
• Children incompletely vaccinated with PCV7: Children aged 24 to 59 months who received 1 or more doses of PCV7 should complete their vaccine series with PCV13.  The age may be extended to 71 months for high-risk children (e.g., sickle cell disease, human immunodeficiency virus (HIV) infection or other immunocompromising conditions, cochlear implant, or cerebrospinal fluid leaks).
• Children completely vaccinated with PCV7: Children aged 14 to 59 months who have received all 4 doses of PCV7 should receive a single supplemental dose of PCV13.  The age may be extended to 71 months for high-risk children (e.g., sickle cell disease, HIV infection or other immunocompromising conditions, cochlear implant, or cerebrospinal fluid leaks).
• High-risk children aged 6 years and older: This permissive recommendation for an off-label use states: "[v]accination with a single dose of PCV13 may be appropriate for children 6 through 18 years of age who are at increased risk for pneumococcal disease".  Healthy older children should not receive the vaccine.
• Additional vaccine for children with underlying medical conditions: Children aged 2 years and older who are at increased risk for invasive pneumococcal disease should receive a 23-valent pneumococcal polysaccharide vaccine after vaccination with PCV13.

Post-marketing studies to include continued monitoring of the vaccine's safety as well as its efficacy in preventing invasive pneumococcal disease and otitis media will be conducted by the manufacturer.

On June 20, 2012, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13) for adults aged ≥ 19 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. ACIP reported as a Category A recommendation that PCV13 should be administered to eligible adults in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23), the vaccine currently recommended for these groups of adults. Adults with specified immunocompromising conditions who are eligible for pneumococcal vaccine should be vaccinated with PCV13 during their next pneumococcal vaccination opportunity.

In pneumococcal vaccine-naive persons, ACIP recommends that adults aged ≥ 19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, and who have not previously received PCV13 or PPSV23, should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later. They further recommended that subsequent doses of PPSV23 should follow current PPSV23 recommendations for adults at high risk, in which a second PPSV23 dose is recommended 5 years after the first PPSV23 dose for persons aged 19–64 years with functional or anatomic asplenia and for persons with immunocompromising conditions. The ACIP recommendations further state that “additionally, those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years, or later if at least 5 years have elapsed since their previous PPSV23 dose.” (Benett et al, 2012)

The ACIP recommendations specify that “adults aged ≥ 19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who previously have received ≥ 1 doses of PPSV23 should be given a PCV13 dose ≥ 1 year after the last PPSV23 dose was received. For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.” (Bennett et al, 2012).