COVID-19 Vaccines for Patients With IBD: A Roundtable Discussion

Gastroenterologists Corey Siegel, MD, David T. Rubin, MD, and Gil Y. Melmed, MD, along with medical resident Jamie Horrigan, MD, who has Crohn disease, discuss the safety and efficacy of COVID-19 vaccines for patients with inflammatory bowel disease, how to talk to patients about the importance and the risks of vaccines, and the questions that remain to be fully answered.

Corey Siegel, MD, is a professor of medicine at the Geisel School of Medicine at Dartmouth University and chief of gastroenterology at Dartmouth-Hitchcock Medical Center in Dartmouth, New Hampshire. David T. Rubin, MD, is the Joseph B Kirsner Professor of Medicine, chief of the section of Gastroenterology, Hepatology & Nutrition, and the codirector of the Digestive Diseases Center at The University of Chicago Medicine in Chicago, Illinois. Gil Y. Melmed, MD, is a professor of medicine and codirector of the IBD Center at Cedars-Sinai Medical Center in Los Angeles, California. Jamie Horrigan, MD, is a medical resident at Dartmouth-Hitchcock Medical Center in Dartmouth, New Hampshire.

TRANSCRIPT:

Dr. Corey Siegel:  Welcome to this roundtable discussion from the "Gastroenterology Learning Network." I'm Dr. Corey Siegel from the Dartmouth-Hitchcock Medical Center, where I'm the Section Chief of Gastroenterology and a Professor of Medicine at the Geisel School of Medicine at Dartmouth.

I'm pleased to bring you this discussion today on guidelines, data, and discussion about the SARS-CoV-2 vaccine for patients with IBD. I'm even more pleased to introduce our panelists who all have expertise in inflammatory bowel disease and vaccinations for people with IBD.

On our panel, we have Dr. David Rubin. He is a Professor of Medicine and Chief of GI at the University of Chicago, and he is the Chair of the National Scientific Advisory Committee for the Crohn's & Colitis Foundation. Dr. Gil Melmed is a Professor of Medicine and codirector of the IBD Center at Cedars-Sinai Medical Center in Los Angeles, and Dr. Jamie Horrigan is a is a physician here with me at the Dartmouth-Hitchcock Medical Center but also an expert in Crohn's disease because she has Crohn's disease and has lived through this pandemic.

With all the same concerns, many patients with IBD have expressed about the safety of vaccination, particularly when on biologic medications, which will really be a big part of our discussion today. Thank you all for joining us this afternoon.

To remind everyone, we made recommendations with the International Organization for IBD (IOIBD) back in December before vaccinations where even widely distributed and maybe even before they are approved in the United States.

For those who aren't aware, IOIBD has 60 International members from 27 different countries who are all specialists in inflammatory bowel disease and really thought through what can we do to help take on this international health crisis, and we couldn't wait months or even a year until we had enough data.

We had to help protect our patients and think through very carefully about the safety and effectiveness of these vaccinations in our patient population. We convened a panel of specialists from IOIBD and other experts.

We reviewed all the data that we had about SARS-CoV-2 vaccinations and other vaccinations and people with IBD and try to come up with our best recommendations with the available information that we had.

We had 64 panelists who joined us including a world-class vaccine expert and really a brief summary of our recommendations -- before I go to our panels -- that patients with IBD should be vaccinated against SARS-CoV-2.

The best time to administer SARS-CoV-2 vaccination in patients with IBD is at the earliest opportunity to do so. Vaccines including all the available vaccines approved here in the US, we believed were safe to administer to patients with IBD and that SARS-CoV-2 vaccination should not be deferred because a patient with IBD is receiving immune-modifying therapy.

Then, finally, patients with IBD who are vaccinated should be counseled to think about vaccine efficacy could be decreased when receiving systemic corticosteroids. Gil, let me start with you. We didn't know much back in early November when we started thinking about this project.

These data were published in the journal Gut in January, where we still didn't have that much more information. Now, a few months later, we're gathering information. If we were to go back in time and think about what we know now, do you think we would have changed anything?

Dr. Gil Melmed: Thanks, Corey. It's a good question. Certainly, at the time, we didn't have the information that we have today, and I'm sure, in three months, in six months, in nine months from now, we're going to have more information. We certainly did our best with the information that we had at the time.

For those key principles that you outlined, IBD patients should get vaccinated. It doesn't matter if they're on medications. The timing of vaccines shouldn't interfere with those medications. The possibility that being on the medications may decrease the efficacy, all of those still ring very much true today.

So far, with the data that's emerged from a couple of centers around the world, we've seen that the actual antibody responses so far seem to be on par with or perhaps a little bit diminished but not that much affected by the medications the patients were on. We're going to continue to learn from that over time.

Also, safety-wise, the signals that were coming through are that the vaccines appear to be as safe in somebody with IBD on medication as they were in the clinical trials. The message certainly for getting vaccination, irrespective of whether you're on medications and the timing of those medications, still rings true today.

Dr. Siegel:  All right. Thanks, Gil. Jamie, let me ask you a question. As someone with Crohn's disease and also a physician who's very thoughtful in the patients that you see in your practice, and I know you're also very busy on social media, so what are other patients saying about getting vaccinated?

What should providers such as ourselves and some of the listeners know that patients have about either fears or enthusiasm about vaccination for SARS-CoV-2?

Dr. Jamie Horrigan:  Sure. I did a quick poll on social media, and a couple hundred people answered. Most people are excited and grateful to get the vaccine, and most people jumped at the vaccine as soon as they could. There were some concerns, though.

Some of the positive comments I got were, "I have colitis. I received my second dose two months ago. I have not noticed any change in GI functioning. I received mine as soon as I could. I didn't have any concerns as I knew getting COVID would be so much worse."

Then we had some women who were pregnant and fully vaccinated, fully vaccinated and breastfeeding, and then some women doing IVF and vaccinated. I think that was important to hear from those people as well.

Some felt very comfortable getting the vaccine after talking to their GI and their colorectal surgeon, and then some of the concerns were that the vaccine might cause some inflammation and may provoke or worse than a flare. This person had been in remission for two and a half years and didn't want to mess that up.

Others are concerned about that "New York Times" article that suggested that those on infliximab might have lower antibody production from the vaccine. A lot of patients on infliximab are understandably concerned about that.

People are concerned also about getting sick from the vaccine and doing well right now, but not wanting to have a vaccine reaction.

Dr. Siegel:  Let me ask you one follow-up question, then David, I want to come to you about that New York Times article and the reference to the study that they had talked about there.

Jamie, do you think, by and large...These are thoughtful questions that patients are asking that, to be honest, we don't have all the answers yet, and we hope to get it, but by and large, are people getting vaccinated, or are they hesitant and waiting?

Dr. Horrigan:  I think most are getting it and excited about it, but there is a small percentage that is concerned and not getting it, or maybe only getting one shot.

Dr. Siegel:  Great. Well, thank you. Really helpful comments. David, all of our practices received lots of phone calls after a New York Times article, and it got spread beyond that, that had brought question to the effectiveness of vaccination. Maybe you can fill us in on what they were talking about and the reference of the study that they were referring to.

Dr. David Rubin:  Thanks, Corey, and I want to echo what Jamie said because in our busy practice here, our patients have, for the most part, been excited to get the vaccine, and we're grateful that most of them now appear to be vaccinated or are getting vaccinated.

Corey brought up the New York Times article that appeared on the 15th of April in which the article was trying to outline that some folks who have immune deficiencies, either inherited or acquired through organ transplantation and subsequent immune suppression, or other immune-mediated diseases.

Which included inflammatory bowel disease, might not mount an appropriate immune response to the vaccines and, specifically, the available vaccines.

I want to point out that most of the data we have, if not all of it, are on the messenger RNA two-dose vaccines. There were some challenges in communicating that because, first of all, when we think of patients with inflammatory bowel disease, I want to remind everyone, IBD is a condition of an overactive immune system, not an underactive one.

The baseline condition in people of Crohn's disease and ulcerative colitis is that their immune system is doing too much, and that's why we use immune-based therapies to try and control it. In addition, the targeted approach to management, at least the goal is to control the inflammation but not necessarily immune suppress people.

It's important to remind everyone of that because what we learned quickly in the pandemic, and we've fortunately been seeing throughout over the last year, is that our patients with IBD are not at higher risk to get COVID in general, and if they do, they don't seem to have outcomes that are much different than the general population.

There are a couple of exceptions, but it's a very important message to start out with because when there's an article that comes out like the New York Times article, that implies that now that we have vaccines, you may not be immune after you get the vaccine.

It feeds right into the fear people have about having these conditions or the uncertainty our colleagues have about giving vaccines to patients who are on these therapies. There's a couple of points I want to make to clear this up.

Number one is that patients with immune-mediated diseases, and very specifically, inflammatory bowel disease are not the same as people who've had organ transplants that are immunosuppressed or who have inherited or other acquired immune deficiencies, and the article lumped everyone together.

Number two, talking about measurable antibodies after someone had a SARS-CoV-2 infection, and then saying that because the antibodies weren't as detectable in people who have these conditions, they therefore are likely not to respond to a vaccine, is absolutely untrue.

The way the vaccines stimulate our immune system and the way they work is not the same as a sustained or durable immune response after an innate infection. That comment and that implication in the article was wrong.

Number three, the article mentioned a very nice study that was done by our colleagues in the United Kingdom. It was called CLARITY IBD. They've done a great job, but they misquoted the study and misrepresented it.

What that study showed is that people receiving infliximab and anti-TNF therapy who received one dose of the two-dose vaccine, the two-dose messenger RNA vaccine, do not have a full measurable antibody reaction, but when they got the second dose or if they had had COVID, and when they had the first dose, either way, when they had two hits, they had a full response.

The New York Times article neglected to mention that part, that if you actually got the two doses, you're going to be protected, or at least those antibody titers will be appropriate.

Leaving it out there as if you are on infliximab and, by extension, other medicines who treat our immune system, you're not going to have an appropriate immune response to the vaccine is very confusing. The main message was if you get the two doses as they're recommended, you're going to have an appropriate immune response.

My final point to clear this up is that the antibodies that were used to measure the immune response were the nucleocapsid antibodies, which are more sensitive for people who've had an innate infection. They're not the anti-spike antibodies, which are the ones that we want to measure in relation to the vaccinations. There were a lot of problems with that.

The bottom line for our colleagues and for patients who hear this is that the data emerging that Gil just summarized show us repeatedly that the two-dose vaccines are safe and that they appear to be equally effective in our patients. We continue to recommend them to everybody.

Dr. Siegel:  Thanks, David. That's a great summary. Gil, the CLARITY study that David was talking about is one of many studies going on. Can you fill us in a little bit about other ways that we're going to be able to learn more about this over the next few months?

Dr. Melmed:  Sure. There are several initiatives going on around the country and around the world. The ICARUS study out of Mt. Sinai in New York recently published a small series of about 50 patients with IBD. Their antibody response is showing that they're absolutely comparable to those without IBD, regardless of whether they were on biologic therapies or not.

That's an early signal. That is very encouraging. We will see more as time goes on. There's the Prevent COVID study out of University of North Carolina. Then we hear Cedars also have launched this study called the CORALE IBD study.

That's a registry right now. We have over 1,500 patients around the country that have signed up. We're eager to enroll anybody who is interested. It's an online enrollment. What we're learning is the side effect and safety profile of these vaccines as well as the efficacy with measurements of antibodies, which will be occurring over time.

What Dr. Rubin just summarized was early data, because that's where we're at. I think six months from now, a year from now, we're going to need to continue to update our knowledge. What do these vaccine responses do over time? What do antibody levels actually mean? We don't even know what antibody levels actually mean.

What is the proper threshold for an antibody to be protective against COVID? Maybe antibodies aren't even the whole story. Maybe we need to be looking at other components of the immune system like T cell, which we're doing in our CORALE study.

We're investigating that right now to see what the correlation is and maybe the T cell function that's more important than the actual antibody levels. Many questions that need to still be addressed that we will be addressing through these various studies going on around the world and updating our knowledge as time goes on.

Dr. Rubin:  And, of course, ultimately, outcomes like, do people get COVID...hospitalization or, God forbid, death.

Dr. Melmed:  Absolutely. That's ultimately what we need to understand. What does a vaccine mean? What does an antibody response mean? What do all these things mean in the context of, of course, getting the infection? That's going to take time.

Dr. Siegel:  So thankful for all the groups that are collecting all this data. We're going to be a lot smarter in a few months. We're a lot smarter now than we were months and a year ago on this.

Jamie, you had brought up that patients have a lot of questions about the impact of the vaccine and on IBD symptoms. Can you express what sort of things you think patients are concerned about? Then Gil, I'm just going to come back to you and ask if that's something that you might be able to get an answer from CORALE or other studies.

Dr. Horrigan:  Patients are concerned that this vaccine is creating an inflammatory response in the body, and that might trigger a flare. As we've talked about before, people with IBD, their immune systems are overactive. There is that concern there. That's the main concern that patients have, is going into a flare or worsening a flare.

Dr. Siegel:  Gil, are we going to be able to answer that question with some degree of confidence over the next few months?

Dr. Melmed:  Yeah, that's the goal. Jamie, I think you bring up a point that we hear all the time from our patients. That's been a concern about vaccines before COVID as well, the concept, "Does a vaccine somehow has to stimulate part of the immune system? By doing so, do we overstimulate an already active immune system?" as David explained to us.

That remains a theoretical concern so far. Oh, by the way, one other point to make is that it's very hard to distinguish GI symptoms after a vaccine from a true flare of IBD. We know from the mRNA clinical trials that an insignificant proportion of patients experienced nausea, vomiting, diarrhea, abdominal pain, which are all potential symptoms of an IBD flare.

How do we truly tease that apart and unravel that? That's one of the things that we're studying in our CORALE registry. What we've learned so far is that, yes, maybe there are slightly more GI symptoms in patients with IBD, but they go away quickly. They're typically on par with what we see in the non-IBD population as well.

What we're learning so far is reassuring. Being able to study it formally across all of these registries will truly give us a sense of that. I consider what we've so far as very reassuring, that even if you get some GI symptoms after vaccine it's not necessarily an IBD flare, and they tend to resolve within a short period of time.

Dr. Rubin:  I completely agree. I'll add, aside from the anecdotal experience of my large practice, that I haven't seen any relapses. Gil's point that when somebody has expected reactions to the vaccine that might include GI symptoms as short-lived is different than someone who has a relapse which, by definition, IBD usually is longer lived and requires an intervention to treat it.

Also, mechanistically, the part of the immune system we try to stimulate with vaccine, specifically these vaccines but also from the long history of data we have on vaccinating our patients with IBD, much of which Gil has contributed and have been the leader in, we've never seen that trigger immune relapse of the disease of the IBD.

We should be reassuring folks that that's not expected. It hasn't been seen yet. It doesn't necessarily even make biological sense. We want to get past that and make sure they get protected.

Dr. Siegel:  Great. David, we're just about to wrap up. Let me ask you one parting look into the future of what your thoughts might be. In 6 months from now, 12 months from now, for our patients with IBD, what does this look like? Is it checking titers regularly? Is it booster vaccinations?

I know we're going to learn a lot based on what you and Gil and Jamie have told us, but what's your vision for how things probably look in six months from now?

Dr. Rubin:  One of the goals of a massive vaccination program is to eliminate the infection from the population. I don't think in 6 months or even 12, unfortunately, that's going to have happened. We may be better in the United States than other places around the world.

If that were to happen, then the idea of booster vaccines or other programs become less important. In the absence of achieving that goal, which is what we want, but probably won't be at, then we need to know what is the durability of immunity. There are two schools of thought.

One is that this might be like the measles vaccination, where it's going to last, and where you may not have as measurable titers, but if you were exposed to the antigen, in this case, spike protein which is the coronavirus, your body will respond properly and protect you.

The other is that we don't know quite enough about this yet, and we probably would err on the side of caution, and people are going to need a booster shot. The booster will look like the second shot we already received, and then we'll study what happens from there. I don't think I can tell you, I don't have the crystal ball here to tell you what is going to end up happening.

I honestly believe that the first part of this story will come from the follow-up from the pivotal trials that got them their Emergency Use Authorization in people without IBD. We'll have to see and learn from that and then go from there. Gil, I'm sure you have some insights here.

Dr. Melmed:  David, as you say we don't know. It could end up that we have lasting protection from the initial dosing or it may require a booster, or it may require ongoing boosters. COVID-19 or this virus, SARS-CoV-2 virus is here. It's not going away probably in our lifetimes. We will be dealing with it in one way or another.

If not, then simply to keep it suppressed from the population. How long these protections last after vaccination, we don't know, but we will be learning over time.

Dr. Siegel:  Should we be checking viral titers or anti-spike antibodies in our patients, Gil?

Dr. Melmed:  At this point, I think it's still in the realm of research because we don't know what it means. We are checking them as part of our study. We're checking both spike protein and anti-nucleocapsid protein and antibody responses so that we can distinguish natural infection from vaccine responses.

There may be others to check as well, but at this point, it's probably in the realm of research. I have patients calling and saying they're interested to know what are their titers after vaccination.

My response to my patients is, "Well, we don't know what it means. Even if you come back with undetectable antibody, we don't know that you're not protected, and there's no impetus or indication to get another vaccine now." There's no practical yet implication for that. Over time, I think we will eventually learn what those mean, and those recommendations may change.

Dr. Rubin:  No, I agree with everything you just said.

Dr. Siegel:  Jamie, as a final comment maybe to our colleague physicians out there talking to patients with IBD, maybe you can just give us a final thought. What should we be telling them? How can we help support our patients and make them confident about what we're doing here?

Dr. Horrigan:  I think continuing to encourage patients that with IBD, you are not at increased risk of more severe COVID. The vaccine is safe. Pretty much everybody with IBD should get it. We're continuing to study vaccine responses in people with IBD, and just the constant encouragement would be helpful for people with IBD.

Dr. Siegel:  Great. Jamie, thank you. Gil, David, thank you for joining us for this roundtable discussion from the Gastroenterology Learning Network. We hope you've learned something, and we look forward to coming back and giving you an update on all of the data that we just learn, and we'll be accumulating over the next few months. Thank you all.