IBD Drive Time: SECURE-IBD Registry and PREVENT COVID

In this, the second IBD Drive Time podcast, hosts Raymond Cross, MD, and Millie Long, MD, are joined by Michael Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina, who helped to create the SECURE-IBD Registry and is studying the efficacy of COVID-19 vaccines among patients with IBD being treated with immune-suppressing therapies.

Raymond Cross, MD, is a professor of medicine and director of the IBD Program at the University of Maryland School of Medicine. Millie Long, MD, is an associate professor of medicine and director of the Gastroenterology and Hepatology Fellowship Program at the University of North Carolina at Chapel Hill.

TRANSCRIPT:

Dr. Millie Long:  Hello, and welcome to IBD Drive Time. My name is Millie Long, and my cohost, Ray Cross, is with me as well. We're very excited to have our guest for this session, Dr. Michael Kappelman.

Mike is a pediatric gastroenterologist and epidemiologist at UNC. He focuses on comparative effectiveness and outcomes research in inflammatory bowel disease.

Most recently, he's the principal investigator of the SECURE-IBD registry of COVID-19 infection outcomes and patients with IBD, and also the co-PI of the PREVENT COVID registry, a study of the efficacy and safety of COVID vaccination and patients with IBD. We'll be focusing on these topics over the next 20 minutes or so.

First off, Mike, I just wanted to start off with some of the data from SECURE-IBD. You guys have published a bunch in this area and really helped us with the understanding of COVID infection. Can you summarize our current understanding of risk factors for severe COVID-19 outcomes in patients with IBD?

Dr. Michael Kappelman:  Absolutely. Thanks again for having me on the show. It's amazing how much we've learned about the effects of COVID-19 on patients with inflammatory bowel disease over the last year, in large part, due to the amazing and robust collaboration of the international IBD community. Our group and colleagues at Mount Sinai in New York established SECURE-IBD in March of 2020, in the beginning of the pandemic.

Providers from across the world submit cases of confirmed COVID-19 in IBD patients and report a number of characteristics, including patient characteristics and demographic factors, disease characteristics of the IBD itself, including medications and other treatments, as well as the outcomes of COVID-19 infection.

To date, over 6,000 cases have been reported to the registry worldwide. So really it’s an amazing collaboration and an amazing amount of data amassed in a short period of time.

What we've learned is that the risk factors for severe COVID amongst IBD patients are generally the same as in the general population—namely, advancing age and non-IBD comorbidities. Older individuals and individuals with greater numbers of comorbidities are disproportionately affected.

The converse is also true. The clinical course of COVID-19 amongst children remains relatively mild. Very few pediatric IBD patients who develop COVID require hospitalization, and an even smaller number require mechanical ventilation or other very intensive supportive therapies.We have seen a handful of cases of MIS-C in the pediatric IBD population; too soon to say whether or not there's any particular risk of that rare COVID-19 complication.

In terms of IBD characteristics, the only immunosuppressive medications that we've consistently seen a signal for its increased risk are the corticosteroid medications and particularly systemic corticosteroids like prednisone. The entero-release budesonide preparations appear to be associated with a slightly increased risk but really to a trivial degree compared with systemic corticosteroids.

None of the other medications have consistently been associated with an increased risk of severe COVID-19. This is really quite reassuring to the millions of patients worldwide with inflammatory bowel disease treated with immune-suppressive medications.

Dr. Long:  That's great inflammation. It's so important to share that with our patients. We, as providers, obviously, we always like to try to avoid steroids, but this is one more reason to potentially try to avoid steroids in particularly those high-risk populations, so it's so important as we move forward.

I want to shift gears a little bit, because you've talked so much about COVID-19 infection and go to the lens of prevention. Obviously, right now, we do have 3vaccines available for COVID-19 here in the United States. Obviously, there are others internationally as well.

I was curious about your thoughts on COVID vaccination and your patients with IBD. Is this something that you recommend —obviously you’re pediatrician—that there are now emergency use authorizations for 12 to 15 as well? Talk a little bit about whether there are any differences by age.

Dr. Kappelman:  The short answer is yes. I do recommend COVID-19 vaccination to all patients, as soon as they are eligible, largely because I think that the benefits of vaccination far outweigh the risks. The long answer is that we really don't know. All patients with immunosuppressive medication treatment were excluded from all of the clinical trials for Pfizer, Moderna, J&J, AstraZeneca, and the list goes on.

And since the majority of inflammatory bowel disease patients are treated with one or more immunosuppressive medications, we really don't know much about the effectiveness or potential for harm of COVID-19 vaccination in this population. And for sure, more study is urgently needed.

But I know many international inflammatory bowel disease organizations and societies, when thinking about weighing the risks and benefits, feel strongly that the risks of vaccination are low, the benefits are potentially great, that COVID itself can be severe, particularly again in older patients or patients with multiple comorbidities, and given the general safety profile of all of the vaccines that are available.

The answer is yes, please do get your COVID shot as soon as you can.

Dr. Long:  No, I can't agree more. I think my cohost, Ray Cross, is going to delve into one of the studies you're working on the PREVENT COVID study. It's going to help us to learn a lot more about vaccination outcomes in patients with IBD.

Before shifting to that, I have one last question, because I'm getting this question all the time from my patients. Many of them are portal messaging me or calling and leaving messages saying, "Hey, Dr. Long, I got my vaccine. Should I go out and get one of those antibody tests that are available on LabCorp and Quest and other places across the country?"

Can you teach us a little bit about those antibody tests and what should we be telling our patients?

Dr. Kappelman:  There are a number of different types of antibody tests that are available. Some tests measure antibodies against the spike protein, that nice pretty little protein that we see all over the Internet. Those antibodies will measure either a response to immunization or a response to prior COVID infection.

Other antibodies and particularly antibodies against different proteins such as the nucleocapsid protein will only detect prior native infection but do not detect response to immunization. Most of the immunizations that are available today target the spike protein itself. Therefore, the immune response is very specific towards that spike protein.

If one were to order or check a vaccine or an antibody titer to measure response to vaccine, make sure that you're ordering one that is against that spike protein. Some of the antibody tests are qualitative. In other words, you get a positive or negative. Others are quantitative or semiquantitative, where you get an absolute number or titer. Those quantitative or semiquantitative tests can certainly be used to measure a humoral immune response to the vaccination, but that clinical interpretation of those tests really has yet to be elucidated.

We don't know what degree of antibody response is required to trigger protective immunity. Simultaneously, in patients who do not have a measurable immune response to antibodies, are there other immune responses that may offer some degree of protection, including cell mediated immunity.

I think all that remains unknown regarding antibody tests, but there's an important differentiation between whether it's a test to the spike protein versus the nucleocapsid or another protein that is not covered by the vaccine.

Dr. Long:  It's such a great point. Even just last week, I had a patient who told me, "Oh, I went out and got an antibody test, and it's negative. What do I do?" I looked at the test, and it was actually one of the nucleocapsid tests.

I think as providers, we have to be aware, and we need to understand what these various tests are and which ones actually wouldn't be measuring a potential response to vaccines, but it's a great point. I think something really clinically relevant.

I know they're more questions generated now I think about vaccination and patients with IBD. I'm going to turn it over to my cohost, Ray Cross, because I know he has some questions about the big study PREVENT COVID that's ongoing.

Dr. Raymond Cross:  Before I do that, I guess, to you and Mike, what are you telling your patients? Are you testing antibody for them? Are you saying, "CDC doesn't recommend it. You shouldn't check them."? What are you guys recommending, or does it depend?

Dr. Kappelman:  It certainly depends. I certainly discuss it with patients and in my case family members. If I am going to do an antibody test, I'm certainly going to wait until the entire vaccination series is completed.

For many of the vaccines, let's say, a 2-dose vaccine, and then a couple weeks afterwards, usually 2 weeks afterwards before patients are considered fully immunized, and so I certainly wouldn't check any test until at least 2 weeks following the second shot.

Then, we have the discussions about the caveats of...we don't know what level is the right level to confer protective immunity. We don't know whether the absence of an antibody test means that a patient doesn't have protective immunity or cellular-mediated immunity, and so I think what is it that patients want to learn from these antibody tests, what is it that I may want to learn from these antibody tests.

At this point, there isn't much action to do if a patient has a positive or negative test. I still generally recommend the same— wearing masks, even after immunization, particularly indoors at least for now until community rates and community trends transmission continues to get even lower.

Still, I think outdoors it's probably fine to remove your mask, especially if you're not on top of a stranger, and you've can maintain some degree of social distancing. I don't know that antibody testing changes my behavior or patient behavior, but for those patients who want to know and understand the caveats of interpretation, I am happy to order the test.

Dr. Cross:  Millie, you're shaking your head. Since it's a podcast...

Dr. Long:  Sorry, yes, it's a podcast. I can't shake my head, I'll just say I agree.

Dr. Cross:  [laughs]

Dr. Long. I agree. It's always a conversation with the individual patient. Obviously, some risk factors for reduced immunogenicity to other vaccines include an older age, age-related, a reduced response, and then medications to some extent.

I want to learn from Mike about what we've learned thus far, but obviously, if someone has been on high-dose steroids, I wonder if they really would mount an appropriate response individually talking to the patients about those risk factors and determining if that quantitative test would change our management moving forward.

Dr. Cross:  It's a good point, Millie. Before I start asking Mike some additional questions, I just want to remind our listeners that this podcast is produced by the Gastroenterology Learning Network and Advances in IBD.

I want to remind those listeners also that we have an AIBD regional virtual course coming up in Houston on June 19. If you haven't registered for that excellent course, please do.

I want to thank Mike before we end, in case I forget, for all the work he's done with the SECURE-IBD registry. COVID has been terrible for all of us and trying to manage our patients was a complete mystery. I use SECURE every day in counseling my patients. I believe our outcomes have been so good because of that. Congratulations, Mike, to you and your colleagues.

There are a couple publications that came out. One was an editorial in the New York Times talking about patients with immune suppression and their inability to respond, to mount a serologic response to COVID.

The other was a recent paper in Gut was a European study showing that patients treated with infliximab didn't respond as well to the vaccine as vedolizumab. Mike, before we talk about prevent COVID, what's your take on those studies?

Dr. Kappelman:  I think all of this highlights the need for data and then need for more information in that population of patients who are treated with immune suppressive medications and who were excluded from all of the initial clinical trials of all of the different COVID-19 vaccines.

Theoretically, it stands to reason that patients who are taking immunosuppressive medications may not respond as robustly to immunizations, whether it be COVID immunizations, influenza immunizations, or other immunizations.

This is an area that we have a huge thirst for knowledge because many patients are treated with immunosuppressive medications, whether it be for organ transplant or chemotherapy for cancer or a number of chronic immune mediated conditions. We're beginning to see emerging data, and we're beginning to see in many ways an overreaction or over-hype to emerging data as is always the case.

It's worth mentioning that not all immunosuppressive medications are the same. Immunosuppressive medications have different mechanisms of action and different levels of immune suppression. So the degree of immune suppression in a solid organ transplant patient is very different than the level or type of immune suppression, that is required to treat a patient with inflammatory bowel disease, or rheumatoid arthritis, may be different than the immunosuppressive regimen to treat a patient with multiple sclerosis or a different rheumatologic condition, and so not all immunosuppressive medications are equal.

The study that you referenced in Gut was one of the early studies in the inflammatory bowel disease population and measured antibody response to patients taking infliximab and anti-TNF biologic therapy, and in those taking vedolizumab or an anti-integrin biologic therapy and focused largely on vaccine response after the first dose of either of the vaccines.

I mentioned earlier on the podcast, that's not as clinically relevant of a time point as measuring immune response a couple weeks following the second dose of vaccine. All of the vaccines that are available are highly potent, particularly the mRNA vaccines.

There's a reason why they are approved as 2-dose series. It's because for many patients that second dose is required to stimulate a sufficient immune response. In that one Gut study that you referenced, when they looked at the subgroup of patients who had both vaccines, most of them regardless of treatment did have an adequate immune response.

My take-home message for all of this is, if you are going to get the vaccine, which I do recommend regardless of immune suppressive therapy, complete the entire vaccination series. Don't stop after the first dose. We need more data specifically on inflammatory bowel disease patients and specifically, comparing and contrasting the medications that are commonly used in that population.

Dr. Cross:  Unfortunately, that wasn't—what you just summarized so nicely—wasn't the message that came from that study, unfortunately. It's a perfect segue to talk about PREVENT COVID. Mike, why don't you tell us about PREVENT COVID and then share whatever results you can share with our listeners?

Dr. Kappelman:  Absolutely. PREVENT COVID is a study that Dr. Long and I and others on our team launched in early 2021 to analyze the effectiveness and safety of COVID-19 vaccinations, specifically in patients with inflammatory bowel disease. It is a real-world down and dirty study where we are trying to recruit as many participants as possible, who have received at least one and hopefully, will go on to receive 2 doses of the Pfizer or Moderna vaccine or one dose of J&J vaccine and will continue to follow patients in the US who receive other vaccines as they are approved under emergency use authorization as well.

We recruit patients in a direct-to-patient fashion where patients can go online and sign up on our project website, www.ibdpartners.org/preventcovid. We also will be launching recruitment at about a half a dozen clinical sites throughout the United States later this month and into July as well.

We follow patients with online surveys at regular intervals to assess medications that patients are using to treat inflammatory bowel disease, side effects from COVID-19 vaccinations, the development of COVID-19 or COVID-19-like illness, as well as any changes in the course of inflammatory bowel disease in the 18 months following COVID-19 vaccination.

We also offer to all participants the opportunity to get an antibody test through LabCorp at 2 time points throughout this study—at about 3 months following the first vaccine, that should correspond to a couple of weeks after the second vaccine or that first clinically relevant time points, and then again, about a year later to see whether that antibody or humoral immune response is persistent over time.

All of those results from the antibody testing are provided back to patients so that they can have a copy of those results and discuss with their physicians as well. We try to make data available to the public as quickly as possible. As a matter of fact, there's a results tab on that study website where updated data regarding recruitments and characteristics of the study population, initial side effects to immunizations, are posted online.

We also posted updates— the overall vaccine response amongst study participants, the overall immune response to vaccines amongst study participants. What we're seeing across the board, 95% of inflammatory bowel disease patients do mount a detectable immune response following that second vaccine dose.

Dr. Cross:  Any subgroups, Mike, didn't do as well with the vaccine?

Dr. Kappelman:  We're in the process of analyzing those subgroups now, and please stay tuned.

Dr. Cross:  Okay. Mike, that was phenomenal. Before you go, for the listeners, can you tell them something about yourself that they may not know?

Dr. Kappelman:  Boy, [laughs] that's always a tough question. Fun fact about Mike Kappelman. In high school, I was a black belt in Tae Kwon Do but have not practiced in over a decade. You probably don't want me on your side if you get into a bar room shuffle.

Dr. Cross:  I don't know if I'm in a tough DDW presentation, I might want you standing right next to me.

Dr. Long:  [laughs] I agree.

Dr. Cross:  Mike, that was awesome. Thank you so much. I'm sure the listeners learned a ton, as did Millie and I.

For our IBD Drive Time listeners, I hope you enjoyed this. Stay tuned. In 2 weeks, our visiting faculty will be Jim Lewis from University of Pennsylvania talking about diet and IBD and the results of the DINE-CD study. Stay tuned. Thank you very much.