Dr. Kates underscored, however, that immunosuppression is not a contradiction for non-live vaccines, including, among others, the COVID-19 vaccine, the injectable flu vaccine and vaccines for respiratory syncytial virus, pneumonia, shingles, tetanus/diphtheria/pertussis, hepatitis A and B, human papillomavirus (HPV) and meningitis.
Getting It Right: Tailoring Immunomodulatory Strategies
Dr. Park drilled down to specifically address concerns that rheumatologists and their patients may have about vaccines given their immunosuppression. Among the key concerns are whether patients will have a satisfactory response to a vaccine, whether the vaccine response can be sustained and the effect of immunosuppression therapy on vaccine efficacy and safety. He said the primary concern is that a vaccine may induce a disease flare of underlying disease.
Dr. Park underscored, however, that although vaccine response is affected by a number of nonmodifiable factors (i.e., age, sex, intrinsic function of T, B and APC cells, and such underlying diseases as leukopenia), a number of modifiable factors can be adjusted to optimize vaccine safety and efficacy in these patients. The modifiable factors include the type of vaccine, adjuvants and dose amount, as well as the type of immunosuppressive therapy.
Taken together, Dr. Park underscored that vaccine response in patients with autoimmune rheumatic diseases can be improved through tailored immunomodulatory strategies. Saying that he once thought that all immunosuppressive drugs induced reduced or suppressed immune response to vaccination, he pointed to research showing that not all disease-modifying anti-rheumatic drugs (DMARDs) are alike. Their effects on vaccine responses differ depending on their mechanism of action with some that do not significantly impair vaccine-induced immune response. Some of these DMARDs include sulfasalazine and hydroxychloroquine, which do not inhibit cell proliferation and therefore do not significantly suppress vaccine responses. Biologic agents that target interleukin-6 (IL-6), IL-7 or IL-12/23 also have minimal impact on adaptive immune responses required for vaccination given their primary effect on innate inflammatory pathways. To date, Dr. Park said no clear indication of the vaccine-suppressive effect of Janus kinase inhibitors has been seen.
However, Dr. Park cited that many commonly used DMARDs are associated with a reduced vaccine response because of their inhibition of lymphocyte proliferation, which is a key step in generating vaccine-induced immunity. These include the antimetabolites, such as methotrexate, azathioprine, mycophenolate mofetil and cyclophosphamide.
Dr. Park used the example of a patient on methotrexate therapy to illustrate how to think about vaccination in these patients, specifically the influenza vaccine. It is well known that methotrexate significantly decreases the response to seasonal influenza vaccine, so he and his team conducted a number of studies to address whether temporarily discontinuing methotrexate, a methotrexate holiday, could reverse methotrexate-induced immune suppression and thereby enhance vaccine response in patients with RA.
