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Humoral Immune Response Detected in Most IBD Patients After COVID-19 Vaccines

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Most patients with inflammatory bowel disease (IBD) develop a humoral immune response after completing an mRNA SARS-CoV-2 vaccine series, according to data from almost 800 patients.

Anti–receptor binding domain IgG antibodies specific to SARS-CoV-2 were detectable in 95% of patients, with “generally similar” results across vaccine type, age group, and medication class, apart from corticosteroid users, who had an 86% antibody detection rate, reported lead author Kimberly N. Weaver, MD, of the University of North Carolina at Chapel Hill, and colleagues.

“Patients with IBD on immunosuppressive medications have the potential for attenuated response to the SARS-CoV-2 vaccination,” Weaver said at the annual meeting of the American College of Gastroenterology.

In support of this possibility, Weaver cited two recent trials from earlier in 2021: one demonstrated blunted antibody responses in IBD patients taking infliximab, while the other showed that full vaccination was less effective at preventing SARS-CoV-2 infection among patients with IBD than nonimmunosuppressed individuals.

To better characterize antibody responses after receiving an mRNA vaccination series, Weaver and colleagues launched the PREVENT-COVID trial, including the present dataset of 787 patients with IBD older than 12 years, all of whom provided serum samples 8 weeks after completing an mRNA vaccine series. Patients with positive nucleocapsid antibody (indicating prior infection), and/or those who reported prior COVID-19 infection, were excluded. Most patients were White (95%) and female (73%), with an average age of 48 years. Slightly more patients received the BNT162b2 vaccine than the mRNA-1273 vaccine (58% vs. 42%).

At 8 weeks, 752 out of 787 patients had detectable antibodies (95%). Antibody rates were highest among patients receiving vedolizumab monotherapy (n = 83; 99%) or ustekinumab monotherapy (n = 102; 99%), followed by mercaptopurine, azathioprine, or methotrexate monotherapy (n = 67; 97%); anti–tumor necrosis factor monotherapy (n = 270; 96%); mesalamine, sulfasalazine, or budesonide monotherapy or no medication (n = 143; 95%); and finally anti-TNF/immunosuppressive combination therapy (n = 75; 86%). Median and mean antibody titers were lowest for anti-TNF combination therapy and highest for vedolizumab.

Thirty-five patients taking corticosteroids had an antibody detection rate of 85.7% (95% CI, 70.6-93.7), compared with 95.9% (95% CI, 94.2-97.1) among nonsteroid users. In contrast, antibody detection rates were not significantly affected by age or vaccine type.

“Reassuringly, most IBD medications do not prevent an initial antibody response after SARS-CoV-2 vaccination, and this is unlike other classes of immune suppression such as B-cell depletion therapy,” Weaver concluded. “Additional data are forthcoming on a larger subset of participants in the PREVENT-COVID study which will allow for analysis of factors associated with humoral immune response and potential optimization of immunization strategies.” She described a dataset of about 500 IBD patients in which booster vaccines overcame poor antibody responses to the initial vaccine series.

“The Data We Need”

Serre-yu Wong, MD, PhD, of Icahn School of Medicine at Mount Sinai, New York, agreed that the findings should offer some reassurance to patients with IBD and their care providers.

Dr Serre-yu Wong

“At the end of the day we have really nice seroconversion rates for the IBD population,” Wong said.

In April 2021, Wong and the ICARUS-IBD Working Group published a similar report of 48 patients with IBD receiving biologic therapies, among whom the seroconversion rate was 100%.

“A lot of the early data, including ours, are on infusion medications, and that’s sort of a practical thing because those were the only patients we could get samples from, but [Weaver and colleagues] were able to get samples from patients not on medications, on oral medications, and on other injection medications that people can take at home, and these are really the data we need for all of our other IBD patients,” Wong said.

Wong highlighted that both trials showed some IBD patients generating “very, very high” titers, many of them above the threshold needed for donating convalescent plasma for COVID-19 treatment; still, exact titer levels needed to protect against SARS-CoV-2 infection remain unclear.

“This is going to require longitudinal studies,” Wong said. “We can’t answer that perfectly right now. We don’t know the magic level of antibodies. I don’t know if you need a titer of 1:100 or 1:1,000.”

Although postvaccination antibody testing is not recommended by the Centers for Disease Control and Prevention, Wong said that “many patients” check their titers anyway, leading to anxiety if antibodies are low or undetectable.

“I know that it’s very disconcerting sometimes when you don’t see an antibody response, and this is one of the hardest things to try to explain to patients,” Wong said. “[It’s necessary] to have a frank discussion about the fact that we don’t know the magic level of antibodies, and that there are also other parts of the immune system that we haven’t tested with antibodies. We haven’t tested the T-cell response, and we do know you can have a T-cell response even if you don’t have a B-cell response.”

Wong suggested that more work is needed to determine the impact of the IBD disease process on susceptibility to SARS-CoV-2 infection, and the rates of antibody responses for the various other vaccines being used around the world.

The PREVENT-COVID study was supported by the Leona M. and Harry B. Helmsley Charitable Trust. The investigators disclosed additional relationships with AbbVie, Johnson & Johnson, Genentech, and others. Wong reported no relevant conflicts of interest.

This article originally appeared on, part of the Medscape Professional Network.

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