Mycophenolate mofetil is also a potential concern, with studies showing a 64% to 73% seropositivity rate and a 31-fold reduction in antibody titers in patients taking the drug.2,4,8 The data associated with prednisone have been more variable, probably partly due to effects of dose variability and the degree of immunosuppression. Studies have shown rates of seropositivity from 64% to 82% and titers dropping from 10-fold to 31-fold.1,2,4,8 The use of glucocorticoids as part of combination therapy with other immunosuppressants also seems to more strongly attenuate immune responses. We don’t know yet if a threshold dose exists for adequate immune responsiveness.8
Other medications, including JAK inhibitors and anti-metabolites, such as methotrexate and leflunomide, have shown more modest suppressive effects on seropositivity and antibody titers, although the reductions vary substantially by study.1,2,4,6,7 Dr. Kim and colleagues also documented a 2.5-fold decrease in antibody levels in patients taking tumor necrosis factor inhibitors.1
Dr. Kim suspects that patients with low or absent antibody responses may be more prone to breakthrough infections, although direct data are not yet available. Data do show that current vaccines are highly effective against the Delta variant in preventing hospitalization and ICU stays among immunocompetent populations. “Whether or not this is also observed in the immunosuppressed with reduced titers of antibodies remains to be seen,” he said.
Dr. Kim pointed out that antibody levels don’t indicate antibody structure diversity. Generating enough antibody diversity may ultimately prove important to one’s ability to neutralize SARS-CoV-2 variants, such as the Delta variant. Dr. Kim and his team are planning to specifically examine the impact of the Delta variant on immune response in patients with rheumatic disease taking different types of immunosuppressants.
Many attendees posed questions about a potential role for vaccine boosters. Dr. Kim speculated, “I think, in the rheumatic disease population, eventually boosters will become part of the armamentarium for providers to mitigate some of the risks from immunosuppression.” But it’s not yet clear which patients may ultimately benefit from such interventions.
ACR Supports 3rd Vaccine Dose for Immunocompromised Patients
On Aug. 13, the ACR issued a statement in support of the recommendation from the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices that rheumatology patients being actively treated with high-dose corticosteroids, alkylating agents, antimetabolites, tumor-necrosis factor (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory receive a third dose of the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines.