On the heels of the announcement of depressed antibody responses to COVID-19 vaccines in transplanted patients, the first question that came to my mind as a practicing rheumatologist was: Does this important and frightening finding also apply to our patients with autoimmune diseases on immunosuppressants?
Fortunately, we have also been studying patients with rheumatic and musculoskeletal diseases (RMD) in our national study of vaccine immune responses. Among 123 COVID-19-naive patients with autoimmune disease — inflammatory arthritis, systemic lupus erythematosus, or other connective tissue diseases — who received a first dose of mRNA vaccine, 74% had detectable antibodies to SARS-CoV-2.
While there were no statistically significant differences between those on immunosuppression compared with those not on therapy, RMD patients on biologic or non-biologic disease-modifying antirheumatic drugs (DMARDS) had an absolute 15% decline in antibody response — 67.5% of those taking biologic or non-biologic DMARDS had detectable antibodies versus 82.4% of those not taking them.
Strikingly, detectable antibodies were identified in only 27.3% of patients on mycophenolate (compared with 70.3% of those taking other non-biological DMARDs) and in just a third taking rituximab (compared with 76.2% for those taking other biological DMARDs).
RMD patients had an overall better antibody response (74%) when compared to transplant patients (17%). While both groups of patients are on immunosuppression, the impact of immunosuppression on vaccine response was not as severe in the RMD population. One reason for this difference may be the fact that RMD patients take a greater heterogeneity of immunosuppressants, many of which did not severely dampen the antibody response.
Nevertheless, there were also similar groups (those on mycophenolate) who had a very low antibody response in both transplant and RMD patients. Until we better understand the mechanisms behind the differential response, any patient who is immunosuppressed should remain cautious even after vaccination. We anticipate the antibody response results following the second dose of the mRNA vaccine will also shed further light on the efficacy of these vaccines in this vulnerable population.
The major implications from our study are that our rheumatic patients are not fully immune after the first dose of the vaccine, and that the response is particularly curtailed in those taking mycophenolate or rituximab. Rituximab is well known to severely dampen antibody responses, and the American College of Rheumatology Vaccine Task Force has provided clear guidelines on the timing of COVID-19 vaccinations with rituximab administration. However, this is not the case for mycophenolate.
Therefore, modified guidelines in holding immunosuppression — when safe to do so — may need to apply more broadly to other immunosuppressants such as mycophenolate. Furthermore, antibody testing can be a very useful tool to assess vaccine response, especially in vulnerable groups, such as those on mycophenolate or rituximab. Lastly, it is imperative that patients with RMDs on immunosuppression talk to their providers before relaxing precautions, even if they have received a vaccine.
Julie J. Paik, MD, MHS, is an assistant professor of medicine and director of clinical trials at the Johns Hopkins Myositis Center in the Division of Rheumatology at Johns Hopkins University School of Medicine in Baltimore.
Dorry Segev, MD, PhD, is a professor of surgery and epidemiology and associate vice chair of surgery at Johns Hopkins University School of Medicine and Bloomberg School of Public Health.
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