CHICAGO—In a particularly fraught landscape of evolving vaccination recommendations at the federal level that often counter state and local health department recommendations, clarifying the need for vaccinations, particularly in subgroups of people for whom safety and efficacy are of some concern given their medical condition, is critical.
What came out loud and clear in the ACR Convergence 2025 session, Strength in Numbers: Using New Vaccines and Data to Protect the Immunocompromised, is that immunocompromised patients, such as those with autoimmune disorders, should be vaccinated against several diseases. “Vaccinate, vaccinate and vaccinate your patients,” emphasized Jin Kyun Park, MD, PhD, professor of medicine and chief of the Division of Rheumatology in the Department of Internal Medicine, Seoul National University Hospital and Seoul National University College of Medicine.
Patients’ families and those close to them should also be vaccinated. Dr. Park urged physicians to not only educate patients on the safety and efficacy of the vaccinations they should receive, but also ensure their patients actually get vaccinated. As of now, he said, rheumatologists are doing a poor job of this, noting that in patients with rheumatoid arthritis, lupus and sclerotic arthritis, only 5% are currently being vaccinated against zoster. “We’re not doing a great job,” he said.1
Why to Vaccinate by Far Outweighs the Why Not
Olivia Kates, MD, MA, assistant professor of medicine in the Division of Infectious Diseases at Johns Hopkins University, Baltimore, laid out why it is important to vaccinate immunocompromised patients. She said the goal is to lower the incidence of infectious diseases, morbidity, mortality and excess cost associated with adverse events. In other words, the goal of vaccination is to increase the safety of patients and ensure the treatments for their autoimmune diseases are successful.
“You [referring to the audience members] are trusted, longitudinal providers who are often overseeing the most important health issue in patients’ lives, managing their immunosuppressive medications and trying to protect them from both their disease and the complications of its treatment,” Dr. Kates said. “By presenting vaccination as a part of the rheumatologic disease treatment plan, you have a great opportunity to make treatment safer and more successful for your patients.”
With few exceptions, most patients with immunocompromised diseases, such as rheumatoid arthritis (RA), should be vaccinated for diseases like the seasonal influenza and COVID-19, Dr. Kates said. One important exception, she emphasized, is that seriously immunocompromised patients should not get live vaccines (i.e., measles/mumps/rubella vaccine, varicella vaccine, intranasal influenza vaccine, oral rotavirus vaccine, oral typhoid vaccine and yellow fever vaccine), although mildly immunocompromised patients can receive them.
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.
Results of their studies consistently showed that withholding methotrexate for one to two weeks after vaccination is sufficient to restore methotrexate-induced suppression of vaccine response, without significantly increasing the risk of RA disease flare.2,3
“Before our studies, it was unclear whether holding methotrexate around the time of vaccination could meaningfully improve vaccine-induced immune response,” Dr. Park said. “Our work was the first to demonstrate that a temporary discontinuation of MTX can indeed restore vaccine responsiveness to flu vaccine in these patients.”
He called the finding unexpected because it contradicted a widely held assumption that methotrexate has a long biologic half-life. Further research, Dr. Park said that in vitro pharmacokinetic studies demonstrated that intracellular methotrexate concentrations declined sharply within 24 hours after drug withdrawal.4 “This indicates that methotrexate is cleared from cells much more rapidly than previously believed,” he said.
Dr. Park emphasized that more clinical research is needed to define the optimal vaccination strategies for each immunosuppression regimen and patient population.
Mary Beth Nierengarten is a freelance medical journalist based in Minneapolis.
References
- Furer V, Weil C, Chodik G, et al. Real-world coverage with influenza, pneumococcal, and herpes zoster vaccines among patients with rheumatic diseases in a nationwide healthcare plan. J Rheumatol. 2024 May 1;51(5):505–516.
- Park JK, Lee YJ, Shin K, et al. A multicenter, prospective, randomized, parallel-group trial on the effects of temporary methotrexate discontinuation for one week versus two weeks on seasonal influenza vaccination in patients with rheumatoid arthritis. Arthritis Rheum. 2023 Feb;75(2):171–177.
- Park JK, Kim MJ, Choi Y, et al. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: Post hoc analysis of a randomised clinical trial. Ann Rheum Dis. 2019 Sep;78(9):1283–1284.
- Park et al. Unpublished research. ACR Convergence 2025, Chicago.
