New research presented this week at ACR Convergence, the annual meeting of the American College of Rheumatology, shows that people with chronic inflammatory diseases, such as rheumatoid arthritis (RA), who take immunosuppressive therapy appear to have an impaired immune response to SARS-CoV. -2, Coronavirus vaccines that cause COVID-19. Patients currently on glucocorticoid or B-cell-depleting therapy appear to have severely impaired response to the vaccine (Abstract No. 0457).
People with chronic inflammatory diseases are often treated with immunosuppressive therapy, but these medications can increase the risk of severe COVID-19 disease. New mRNA-based vaccines against SARS-CoV-2 could provide powerful protection for these at-risk patients. In this new study, the researchers wanted to find out how effective the new vaccines would be for these high-risk patients and to divide their risk of having impaired immune responses to COVID-19 based on their immunosuppressive therapy.
The results of our study support several important conclusions. First, nearly 90% of patients who take immunosuppressants to treat systemic autoimmune diseases can escalate antibody responses. Second, however, the overall antibody titer was decreased by about threefold compared to those not subject to immunosuppression. Finally, some drugs aggressively reduce antibody titers, such as B-cell-depleting agents, glucocorticoids and JAK inhibitors. “
Alfred Kim, MD, PhD, assistant professor, division of rheumatology, at Washington University School of Medicine, St. Louis and co-author of the study
To assess the immune response to the vaccine and adverse reactions in people with chronic inflammatory diseases, researchers collected blood samples from 197 adults with chronic inflammatory disease and 53 immunocompetent controls before the first vaccine dose and 1-2 weeks after the second shot. They measured anti-SARS-CoV-2 spike IgG+ binding and neutralizing antibody titers to assess the magnitude and quality of the patients’ immune response after vaccination.
Compared with patients with competent immune systems, subjects with chronic inflammatory disease had a threefold reduction in antibody titers and neutralization of SARS-CoV-2 to the common D614G variant. Two immunosuppressive therapies appeared to further impair humoral responses to the vaccine: patients taking B-cell-depleting drugs had a 36-fold reduction and patients taking glucocorticoids 13-fold reduction.
Other immunosuppressive therapies also impaired antibody titers, including Janus kinase inhibitors, and antimetabolites, including methotrexate. Targeted therapies for chronic inflammatory diseases, including TNF inhibitors, IL-12 and IL-23 inhibitors, and integrin inhibitors, had only a modest effect on antibody formation and neutralization after vaccination of patients.
Given the ongoing epidemic and potentially severe risks of COVID-19 for immunosuppressed patients, research for this group is ongoing. They are currently trying to determine the cross-matching, long-range antibody, neutralization titers, and T-cell responses of people in this population.
“These results demonstrate that the risk of suboptimal antibody responses is not uniform across immunosuppressed rheumatic patients, and that some populations are at greater risk of poor or absent responses. Strategies to mitigate these declines in patients’ antibody responses while they are on these responses should Identify medications, such as keeping medications around the time of vaccination or possibly using pre-exposure prophylaxis,” says Dr. Kim.
“The results of our study will help clinicians identify those patients at high risk of poor antibody reactions after SARS-CoV-2 vaccination, so that we can screen for those who might benefit from an additional dose of vaccine or prophylaxis before exposure.”
This research was supported by funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
American College of Rheumatology