What to Tell Your Patients With Autoimmune Diseases About the 2020-2022 Flu Season

By Cassandra M. Calabrese, DO (@CCalabreseDO), and Leonard H. Calabrese, DO (@LCalabreseDO)

We head into the 2020-2021 flu season with a great deal of uncertainty, as we truly do not know what flu season will look like this year due to the COVID-19 pandemic. We want to highlight the importance of getting a flu shot this year, realizing it may not be in the forefront of everyone’s minds given the state of the world. While we have some hope that this flu season will be less severe than previous years (with universal masking and social distancing already in place, fewer crowds, etc.), we feel strongly that this year it is more important than ever to maximize uptake of seasonal influenza vaccine. Like with any flu season, the stakes are high for patients with autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and psoriasis) — particularly for those on immunosuppressive therapies. While influenza infects tens of millions of individuals, causes over a half a million hospitalizations and can lead to death in 30,000-60,000 Americans in the general population, the disease carries even greater morbidity in our autoimmune population. Thus, maximizing vaccination coverage is a vital part of overall care.

How to answer common patient questions about influenza

Q: Why is it so important to get a flu shot this season?

A: There are many important reasons to get a flu shot, and this year it is more important than ever because of the COVID-19 pandemic. To start, influenza cases this season are going to complicate the clinical picture when a patient presents with a “flu-like” illness, as they will need to be evaluated for both COVID-19 infection and influenza. Second, vaccination uptake among healthcare workers is of the utmost importance this season, both to protect our patients and to keep ourselves healthy so we can continue to care for our patients.

Q: Where is the best information available concerning vaccination recommendations for patients with autoimmune diseases?

A: While most professional organizations make some broad recommendations regarding vaccines, in patients with specific diseases, the Centers for Disease Control and Prevention is the standard bearer of such information. (Recommendations for patients with autoimmune disease can be found in Table 2, under “immunocompromised” [excluding HIV]). These recommendations emphasize the importance of vaccinating this population because of greater morbidity and mortality from influenza. The recommendation is simple: one dose of either quadrivalent inactivated vaccine or high-dose trivalent or quadrivalent vaccine for those over 65 years of age. Remember, the annual flu vaccine is recommended for ALL patients in your practice.

Q: Will the immunosuppressive drugs my patient is receiving interfere with the safety or effectiveness of flu vaccines?

A: This is a complex question given the multitude of immunosuppressive and targeted therapies we have available. In general, for patients who are not receiving high level immunosuppression, the most commonly used drugs and biologics have no clinically significant effect on vaccine response and therefore pose no practical issue. A major exception is rituximab and other B cell depleting drugs, which profoundly affect vaccine responses; thus, if possible, timing should be adjusted to the nadir of drug administration. Furthermore, since influenza vaccines are killed (i.e., except the live nasal vaccine, which is contraindicated in this population), immunosuppressive therapies pose no additional safety issue.

Q: What about methotrexate? Does it pose special issues?

A: Indeed, among the immunosuppressive drugs widely used to treat autoimmune disease, methotrexate has demonstrated the most consistent capacity to reduce the immunogenicity of a number of vaccines, including influenza. A series of recent studies from a South Korean group has demonstrated that merely withholding two doses of methotrexate following influenza vaccine can boost immune response by nearly 50% with no apparent adverse effects on disease control. While withholding methotrexate in such fashion is not formally recommended by any professional body, it is our practice to do so when at all possible.

Q: Does the high dose influenza vaccine offer advantages for patients with immunosuppressive illnesses?

A: The high dose vaccine (Fluzone High-Dose vaccine) contains approximately four times the antigenic load of virus compared with the standard vaccine and, in healthy individuals > 65 years of age, appears to be more immunogenic and possibly more clinically effective. For the 2020-2021 flu season, a quadrivalent high-dose vaccine is available that contains two A strains and two B strains. Limited studies in rheumatoid arthritis have suggested that the high dose form results in higher antibody titers in all patients regardless of age, which is encouraging. We think this is something to watch but have concerns, as early epidemiologic reporting in the current flu season indicates that B strain infections are predominant in the U.S., which is unusual for this time of year. When these data can be duplicated with the quad form of the high dose vaccine, we believe our enthusiasm will increase considerably for this strategy. Be aware, however, that the high dose vaccine is nearly twice as expensive as the standard dose and private insurance is unlikely to cover it for those < 65 years of age.

Q: What about my patient who tells me they have an egg allergy?

A: Egg allergy is NOT a contraindication to receiving any formulation of seasonal influenza vaccine, including egg-based vaccines. This has been the recommendation since the 2016-2017 Advisory Committee on Immunization Practices (ACIP) update to influenza vaccine guidelines. Even patients with a history of severe egg allergies (e.g., respiratory distress, cardiovascular or GI symptoms) can receive any influenza vaccine under the supervision of a healthcare provider who can recognize and manage severe allergic conditions. In addition recombinant and cell-based vaccines that contain no egg product are available if needed. For this year’s flu season, the recommendations have been updated to remove this latter recommendation if eggless vaccines are given (e.g., Flublok or recombinant vaccine).

Q: Who should not get a flu shot?

A: The only true contraindication to receiving the flu shot is if a patient has experienced a severe (life threatening) allergy to a prior dose of a seasonal influenza vaccine, or in a patient with a severe allergy to a component of the vaccine. A history of Guillain-Barré after a flu shot or any other vaccine is also a contraindication, in our opinion.

Q: What are best practices to increase flu vaccine coverage in my practice?

A: Numerous barriers to vaccine administration exist for patients with autoimmune disease, including decreased awareness by both practitioners and patients, vaccine hesitancy, communication issues between specialties, confusing vaccine series (e.g., pneumococcal), insurance issues or limited stock of the vaccine. Unfortunately, vaccine uptake remains very low in practices treating patients with immune-mediated diseases. A combination of interventions will likely be needed to increase uptake, including systematic interventions directed at both patients and providers (e.g., standing orders, sending reminders in the mail, placing posters in clinic, keeping adequate stock of flu vaccine). Studies have shown that strong physician/provider recommendations have a significant impact on vaccine uptake. We also like to remind our patients that even if they are reluctant to be vaccinated for personal reasons, they should still strongly consider the vaccination in order to protect their friends and loved ones who may be vulnerable. To help this cause, try to carve out a few minutes during each patient visit this flu season to address the seasonal influenza vaccine. For patients who are not interested, try to understand their health beliefs and educate them on the importance of this yearly vaccine.

Q: What should I say to a patient who told me that that last year’s flu vaccine was only 20% effective and who is not interested in getting one?

A: Influenza vaccine efficacy varies from year to year. Studies have shown that even relatively low-efficacy influenza vaccines can have a significant impact on infection prevention within the general population.

Flu season is here to stay. While flu season usually peaks in January and February, and can last as late as May, we just don’t know what it will look like this year. We advocate that our patients get vaccinated as early as possible.