B-cell therapies, mycophenolate worsen COVID-19 vaccine response in inflammatory disease
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Patients with chronic inflammatory disease on immunosuppressants, especially B-cell depleting agents, mycophenolate and glucocorticoids, exhibited poor antibody responses to the mRNA vaccine for COVID-19, according to a presenter here.
“It is well established that patients with various autoimmune diseases who are on immunosuppression are at increased risk for severe manifestations of COVID-19, and also increased risk for breakthrough infections,” study researcher Alfred H. J. Kim, MD, PhD, assistant professor of medicine in the division of rheumatology at Washington University in St. Louis, said during a press conference. “There is [also] emerging data demonstrating that variants do emerge pretty rapidly from those with prolonged SARS-CoV-2 infection and immunosuppression appears to be a leading risk factor.”
To examine the effectiveness of COVID-19 vaccination among patients with chronic inflammatory diseases, Kim and colleagues collected blood samples from patients with inflammatory disease (n=274), as well as healthy control participants (n=53), prior to their initial immunization and 1 to 2 weeks following their second immunization. The researchers then evaluated serum anti-SARS-CoV-2 spike (anti-S) IgG binding and neutralizing antibody titers to determine the magnitude and quality of the humoral immune response post-vaccination.
According to study results, patients with chronic inflammatory disease demonstrated a threefold reduction in antibody titers (P=0.0046) and SARS-CoV-2 neutralization (P< 0.0001) to the common D614G variant vs. healthy control participants.
Kim and colleagues reported that, although JAK inhibitors and antimetabolites, such as methotrexate, reduced antibody titers in multivariate regression analyses, patients on B-cell depleting agents experienced a 57-fold reduction in antibody titers at the population level, patients on MMF saw 21-fold reduction and those on glucocorticoids saw a ninefold reduction.
“The risk of reduced antibody responses was not shared equally among the different immunosuppressive classes,” Kim said during the press conference. “We found that B-cell depleting agents, such as rituximab or ocrelizumab, had profound impacts on antibody production. The next group that had the most impactful reduction in antibody titers was mycophenolate or mycophenolic acid; this was first established within solid organ transplant recipients but has been recapitulated in the autoimmune space.”
Kim noted that “the next largest offender of reductions to antibody titers were glucocorticoids, but here we found that the low-dose glucocorticoid users were also unable to mount good antibody responses, so there is some conflict in the literature.”
In comparison, the researchers found that TNF inhibitors, interleukin-12/23 inhibitors and integrin inhibitors, offered only “modest impacts” on antibody formation and neutralization following vaccination.
“Reassuringly, we found that most patients with chronic inflammatory diseases in our study will mount acute antibody responses, albeit at modestly reduced levels, with the greatest association of poor antibody responses found in those on B cell depleting agents, mycophenolate and glucocorticoid users.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Some rheumatology patients have been at risk for COVID-19 post-vaccine due to their treatment with immunosuppressives. This study found that B cell depleting (rituximab), mycophenolate and corticosteroid therapies were the most affected groups with a poor antibody response to vaccine. Patients receiving JAK inhibitors, and methotrexate had decreased responses to the vaccine. This is compatible with previous analyses.
The group plans to analyze T cell responses to the vaccine, and this certainly is a welcome area of study. In their study in Annals of the Rheumatic Diseases, Aletaha and colleagues have previously shown SARS-CoV-2 vaccinated rituximab-treated patients had impaired humoral immunity, but inducible T cell responses. A vaccine study by Painter and colleagues in Immunity has shown a robust T cell response to COVID vaccination.
Additionally, a recent report from Schwarzkopf and colleagues in Emerging Infectious Diseases showed that immunity to SARS-CoV-2 can occur in patients without antibodies if there is a significant T cell immune response. Another study in Journal of Infection indicated that antibodies (as detected by routine laboratory assays) following COVID infection are not essential for protection against reinfection. Further study of our immunosuppressed patients is warranted as we continue to battle COVID-19.
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Kim A. Abstract 457. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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