乌鸦传媒

A topic widely discussed among physicians during the recent Digestive Disease Week virtual meeting was a large British cohort study that looked at the antibody response to SARS-CoV-2 infection or COVID-19 vaccination in patients with inflammatory bowel disease (IBD) on infliximab (Remicade) or vedolizumab (Entyvio).

In this first of four exclusive roundtable episodes, 乌鸦传媒 brought together three expert leaders in the field -- moderator , of Baylor College of Medicine, is joined by , of Michigan Medicine, and , of Yale School of Medicine -- for a virtual roundtable discussion about what they have been telling their patients with Crohn's disease about the study findings.

Following is a transcript of their remarks:

Hou: Hello, everybody. I am Dr. Jason Hou. I am an associate professor of gastroenterology at Baylor College of Medicine. I'd like to welcome you to the DDW Virtual Roundtable on 乌鸦传媒. We're really fortunate to be joined by two panelists here today, Dr. Shirley Cohen-Mekelburg, she's an assistant professor at the University of Michigan, as well as Dr. Jill Gaidos, associate professor at Yale University.

Let's talk about a very interesting topic that's come up, I think, high in the minds of a lot of providers as well as patients right now, related to COVID-19 vaccinations. There is a very interesting study called the , which is looking at antibody response in patients with inflammatory bowel disease who have been on infliximab compared to vedolizumab, and which showed some, again, interesting results in terms of antibody response, immune response, to the two different COVID vaccines. I'd like to open up to the panel about their discussions or thoughts on the study.

Gaidos: Well, first of all, the New York Times [article] about the study resulted in numerous MyChart messages and phone calls to my office about appropriate timing of medications and should they hold their medications before getting vaccines.

I think the key point is even in patients who are not on immunosuppressive therapy, or healthcare workers who are not on immunosuppressive therapies, the first vaccine by itself is not adequate, which is why these vaccines are approved to be given in two separate doses in order to get an adequate immune response. It's the same thing with our IBD patients, whether they're on immunosuppressive therapies or not.

I still stress to my patients, "You don't need to adjust your medications." Again, we don't know, for anyone, whether we're going to require a booster at some point, "How long is this? Are these vaccines going to be effective?" We're kind of all in the same boat here with figuring this out as we go.

Cohen-Mekelburg: Yeah. I agree with Jill. I would say a lot of the media coverage of this has kind of put people in a little bit of frenzy. As everyone's shaking their head, we all have been answering lots of calls and questions recently from patients, which are completely fair.

Just thinking about this study specifically, I think some interesting points are obviously the study was done in the U.K., so while it was looking at their population, our population probably is generalizable to the U.S. I think it's interesting that they included patients who are 5 years and older, kind of as this becomes a question not only of older adults or middle-aged adults, but actually how do children respond to vaccinations.

I think the other interesting point is that this is a real-world study, so the antibody concentrations were not from patients who were included in any of the clinical trials, and so that makes it a little bit more real world in how we're interpreting it.

Yeah. I mean, I think just understanding the study design itself too, in what way it was actually studying, if you will, which is really comparing drug antibody levels ... or not drug antibody levels, vaccine antibody levels in Remicade [infliximab] versus Entyvio [vedolizumab], and so this doesn't necessarily compare all patients with IBD or patients with all the different immunosuppressants, or biologics versus no biologics. I think it's important to kind of think about the results in that context too.

I think one of the big points here is also regarding what do the findings actually mean. I think it was great that they looked at both antibody concentrations and then also at seroconversion in general like, "Do patients develop antibodies? Yes or no?" But I think one of the big topics to discuss is what do these values actually mean. If you have a higher antibody concentration, does that actually mean that you're more protected and what is the threshold? No one really knows.

I know there has been some conversation as well as far as you need to show that you have antibodies to be protected. Or is it one of those things that if you're exposed to an antigen your body is going to start an immune response? I think a lot to be determined.

Hou: Yeah, I agree. I think it does raise some concerns. I think that our job, obviously, is to be careful and think through what are the implications of vaccinations. Which I think today in clinic, I had every patient who had a question about the vaccine, and it is a concern that the patients on the ... just to summarize some of the other details on the ...

After a single dose of vaccine, patients who were on infliximab did have a lower rate of developing measurable antibodies, with the caveats you just mentioned, Dr. Cohen. Compared to vedolizumab, and as we've seen in other vaccine studies, looking at vedolizumab being gut-selective, it's not expected to have any reduction in immune response to a vaccine. I have, in some ways, found that encouraging. That's kind of what we've seen in other vaccine type of studies in terms of a systemic immunosuppressant versus a more targeted one.

But I think one thing that was not the primary goal of the study, but they did include kind of as a footnote at the end, is in the patients who received their second dose of vaccine -- this is, again, what I think both of you were getting at -- that was their rates of seroconversion with measurable antibodies were very similar in the 80th percentile. Which again, keeping context, in other vaccines that we use, they do not provide that level of protection. It's actually higher than we expect with other vaccines that we routinely recommend to our patients.

Those are, I think, some important things to consider. That was just a small fraction of patients, of course, in this study who obtained, who they never followed out past their second vaccines, past their second dose. But that's, I think, an important thing to keep in mind, that maybe there is some attenuation, especially after the first dose that may have an impact on timing.

But with the second dose, it looks like these patients, the infliximab patients, were able to catch up fairly close, if not similar in number, to antibody rates as patients on vedolizumab.

Cohen-Mekelburg: Jason, you bring up a good point too, which is while the objective of the study was to look at the difference between concentrations in both groups, really kind of big picture, this study actually shows us that you get good antibody response in both groups.

Hou: Yeah.

Gaidos: I think one of the questions that this doesn't address is, "What about our patients who are on thiopurines or other immunomodulators?" Because we do know that those are immunosuppressive and they can impact response and seroconversion with other vaccines, so that would have been a nice group to include here.

Cohen-Mekelburg: What are your thoughts on this question of a third vaccine?

Gaidos: A booster, you mean, or ...?

Cohen-Mekelburg: Mm-hmm.

Gaidos: Oh, I think it's coming. I think we're going to ... it's going to be like a flu shot. We're going to get our flu shot and our COVID shot every year. As these new variants come out, I think probably something will develop or mutate that's not covered by the current vaccines and it'll just be part of our routine.

Cohen-Mekelburg: I think this topic, while it's very relevant to our patients, thinking about it not in isolation affects a lot of different patients with different conditions who require immunosuppression. A few of my colleagues here at U of M actually just published a paper that looked generally at the burden of immunosuppressive medications on the U.S. population and they used a large commercially available dataset. They found about 80,000, I believe, or 2.8% of the commercially insured population in Optum was on an immunosuppressant, so this is a definitely a big problem that hopefully we'll have answers to in the coming months.

Gaidos: Yeah. Absolutely.

Hou: Yeah. I think the walkaways for me from this study is that, again, there may be an attenuated initial response to single dose, but after second dose of the vaccine, there appears to be fairly high numbers, high rates of antibody formation, in response to the vaccine. Big unknowns, I think, as both of you alluded to, is we're looking at a number, but what we really care about are infections, how protective is it. So that data is yet to be coming.

Then I think what you mentioned. Dr. Cohen, in terms of the booster shot, is it going to be an annual, as you mentioned, Dr. Gaidos? I think is yet to be seen, so a lot more to come in that field and we're looking forward to additional data as that comes around.

There are multiple studies prospectively looking at vaccines, responses, and complications in our IBD patients that are ongoing, so that prospective data in terms of actual outcomes, not just antibody formation, will be really helpful for us to communicate this to our patients.

Thank you, both of you, for your conversation, for your discussion on this topic, and hopefully the rest of the audience will be able to join us for our additional conversations on other abstracts.

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