May/June 2017

Medication Monitor: Vaccines and Autoimmune Disease
By Mark D. Coggins, PharmD, CGP, FASCP
Today's Geriatric Medicine
Vol. 10 No. 3 P. 5

Vaccine Safety
Current scientific evidence clearly favors the value of vaccinations. Vaccines are the best defense we have against serious preventable and sometimes deadly contagious diseases. Vaccines are some of the safest medical products available, but as with any other medical products, there may be risks. Providing accurate information about the value of vaccines as well as their possible side effects helps people to make informed decisions about vaccination.1 In fact, the Centers for Disease Control and Prevention (CDC) has identified that the most significant barrier to vaccination coverage is a lack of knowledge about vaccines among adult patients and providers.2

Federal law requires that Vaccine Information Statements explaining vaccine benefits and risks be provided when certain vaccinations are administered (including before each dose). Vaccine Information Statements are available in Spanish and many other languages. In addition, more detailed information describing the benefits and risks of vaccines is available in the Licensed Vaccine List from the FDA.1

False Reports
With the advancement and success of vaccines, we hear less about the serious consequences of preventable diseases, and the discussions become more about the risks associated with vaccines. Numerous false reports in the media about potential risks of vaccinations and their association as a cause of autism, autoimmune diseases (ADs), and other serious adverse events have resulted in misinformation and confusion.3

The protective value achieved from receiving vaccines is well established and is based on sound epidemiologic data both for the general population as well as for those individuals with AD. While there is a rare possibility that vaccines may induce or exacerbate AD, the basis for making widespread claims is highly speculative and is based on isolated case reports.4

Autoimmune Disease and Infection Risk
There are more than 80 known ADs, including rheumatoid arthritis, systemic lupus erythematosus, and vasculitis. Overall, ADs are common, affecting as many as 50 million Americans. As a group, ADs are a leading cause of death and disability. Persons with AD have a two times greater risk for infection than healthy individuals. This increased risk can occur as a result of abnormal immune response associated with the disease but also can be attributed to immunosuppressive therapies required to control the activity of the underlying disease and associated organ complications.5

Immunosuppressive Treatments
Immunosuppressive treatments commonly used in AD include the following:6

• corticosteroids or "steroids" (eg, prednisone);

• disease-modifying antirheumatic drugs (DMARDS) such as methotrexate, leflunomide, azathioprine, cyclosporine, and mercaptopurine; and

• biologic agents also referred to as "biologics" or targeted immune modulators such as antitumor necrosis factor agents (eg, etanercept, adalimumab), belimumab, and rituximab.

Biologic agents are distinguished from other immunosuppressives in that they are produced by living systems, such as bacteria or plant or animal cells. As soon as an individual begins using biologics to modify the immune system, his or her immune system's ability to fight off and prevent infection is severely suppressed.6

Biologics and other immunosuppressive agents can increase the risk of infections, including the following:

• bacterial sepsis;

• Mycobacterium tuberculosis infection recrudescence;

• fungal infection/reactivation; and

• viral reactivation, eg, varicella-zoster virus (shingles) or worsening of a chronic viral infections such as hepatitis B infection.

Vaccine Types
Vaccines are typically classified as inactivated "killed antigen" vaccines or as live attenuated vaccines (LAVs). Killed vaccines have no live components in them and are extremely safe and effective, while LAVs contain living virus or bacteria, making them markedly weakened or "attenuated." The virus or bacteria in LAVs will grow in a vaccinated individual, but because they are weak, they will cause no or very mild disease in persons with normal immune systems.

See Table 1 and Table 2 for additional information about vaccine types.

Vaccine Use in Individuals With AD7
Vaccines are generally safe and effective for persons with AD and are recommended by standard vaccination guidelines. Some studies have found mildly impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufficient to provide protection for the majority of immunized individuals. The accumulated data on the safety and effectiveness of vaccines warrant immunization with the majority of vaccines for patients with AD, especially vaccination against influenza and pneumococcal disease. Despite clinical recommendations for vaccination protocols for this population, vaccination rates are low for persons with AD.

This may be due to education about the differences in types of vaccines, inadequate communication between primary care physicians and specialists, patient misconceptions about safety, and fear of flares, which are sudden and severe onset of symptoms. In general, while flares are possible, they are rare when guideline recommendations are followed.

Inactivated Vaccines7
Inactivated vaccines can be administered safely to patients with AD even if they are undergoing immunosuppressive therapy, although the level of protection may be lessened.

Persons with AD who become infected with influenza, pneumonia, or hepatitis B are at increased risk of more severe disease and increased mortality/morbidity than immunocompetent persons. Therefore, persons with AD are strongly encouraged to receive these vaccinations.

Influenza (intramuscular injection), pneumococcal, and hepatitis B vaccines are inactivated vaccines and are safe and generally sufficiently immunogenic in patients with AD.

• Influenza (intramuscular): For patients with AD, a yearly intramuscular (which is inactivated) influenza vaccination is recommended. Patients aged 65 and older should receive the high-dose vaccine, which has been shown to be more effective in this age group.

• Pneumococcal: The CDC recommends vaccination for all immunosuppressed adults naive to pneumococcal vaccinations. The CDC recommends vaccination with PCV13 (pneumococcal conjugate vaccine) followed by PPSV23 (pneumococcal polysaccharide vaccine) in eight weeks to one year later.

• Hepatitis B vaccine (HBV): For patients with AD, the severity of hepatitis B infection is more severe with increased morbidity rates than for persons who are immunocompetent. Therefore, hepatitis B vaccination is of particular importance in patients with AD, as biologic therapy can increase the risk of reactivation in those infected. Before initiating biologic therapy, HBV serology should be checked in all patients. Some experts recommend initiating hepatitis B vaccination at the time an AD is diagnosed.

Tetanus, diphtheria, and acellular pertussis vaccines are inactivated vaccines and, as in the general population, the immunization status of patients with AD should be checked and vaccination considered for tetanus, diphtheria, and pertussis vaccination.

• Tetanus and diphtheria: Tetanus and diphtheria vaccinations are recommended once every 10 years.

• Pertussis: The pertussis vaccine helps protect against whooping cough, which is highly contagious, causing prolonged distinct coughing. Pertussis remains incompletely controlled in the United States and is considered an epidemic worldwide. The pertussis vaccine is recommended in childhood with one booster in adulthood.

Live Vaccines7
Live vaccines (measles/mumps/rubella, oral poliomyelitis vaccine, yellow fever, and varicella zoster) are contraindicated in patients with immune-mediated inflammatory disease who are undergoing immunotherapy. Although the varicella zoster vaccine is a live vaccine and is, as such, contraindicated in immunocompromised individuals, some consider the risk-to-benefit ratio for this vaccine beneficial for patients on low-dose immunotherapy, especially since rescue therapy with acyclovir is possible in case of virus persistence or infectious symptoms after varicella zoster vaccination.

Herpes Zoster Vaccine (ZOS)
This vaccine is recommended for all immunocompetent patients aged 50 or older with AD; however, because ZOS (shingles vaccine) is a live vaccine, it is contraindicated when patients with AD are receiving biologics or high-dose corticosteroids. ZOS should be delayed for a least one month after discontinuation of such therapy.

ZOS can be given to patients with AD even if they are receiving the following:

• short-term, low-dose, or local (eg, topical or nonsystemic administration) corticosteroid therapy; and

• low-dose treatment defined as using methotrexate (<0.4 mg/kg/week), azathioprine (<3 mg/kg/day), or 6-mercaptopurine (<1.5 mg/kg/day) for the treatment of rheumatoid arthritis, psoriasis, polymyositis, sarcoidosis, inflammatory bowel disease, or other conditions.

ZOS does not need to be delayed in these persons, and it can be administered to contacts of patients with AD and other chronic diseases or altered immunocompetence.

Additional Guidance for Live Vaccines7
Remember that LAVs are of greatest concern because of the risk of severe infections following live vaccination of an immunosuppressed patient receiving a biologic drug or high dose corticosteroids.

Persons with AD who are being treated with immunosuppressive therapy must be regarded as immunocompromised individuals, although the extent to which immune competence is impaired depends on the type and dose of medication used, as well as the duration of therapy. Administer LAVs no earlier than three to four weeks before the start or restart of immunosuppressive therapy to ensure that virus replication has ended before impairing a patient's immune competence.

In order to safely administer a LAV to a person with AD with respect to the exact time period after which immunosuppressive therapy has been discontinued, it depends on the type, dose, and duration of the therapy; however, a safe rule of thumb is to allow a period of three months for the immune status to be completely restored, except for corticosteroid therapy, where a waiting period of one month is thought to be sufficient.

— Mark D. Coggins, PharmD, CGP, FASCP, is vice president of pharmacy services for Diversicare, which operates skilled nursing centers in 10 states. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

References
1. Safety. Vaccines.gov website. https://www.vaccines.gov/basics/safety/index.html

2. Williams WW, Lu PS, O'Halloran A, et al. Surveillance of vaccination coverage among adult populations — United States, 2014. MMWR Surveill Summ. 2016;65(1):1-36.

3. Vaccines do not cause autism. Centers for Disease Control and Prevention website. https://www.cdc.gov/vaccinesafety/concerns/autism.html. Updated November 23, 2015.

4. Murdaca G, Orsi A, Spanò F, et al. Influenza and pneumococcal vaccinations of patients with systemic lupus erythematosus: current views upon safety and immunogenicity. Autoimmun Rev. 2014;13(2):75-84.

5. Autoimmune disease. Healthline website. http://www.healthline.com/health/autoimmune-disorders?m=0#treatment6

6. Brause B. Vaccinations and lupus: an update of what you should know. Hospital for Special Surgery website. https://www.hss.edu/conditions_vaccinations-lupus-update.asp. Published June 17, 2014.

7. Rahier JF, Moutschen M, Van Gompel A, et al. Vaccinations in patients with immune-mediated inflammatory diseases. Rheumatology (Oxford). 2010;49(10):1815-1827.