Amy Oxentenko, MD, on Updates in Celiac Disease

Dr Oxentenko gives a look into the future for the treatment of celiac disease, including the potential of therapies to offer alternatives to the gluten-free diet.

Amy Oxentenko, MD, is a professor of Medicine and vice dean of Practice at Mayo Clinic in Rochester, Minnesota.

Hello everyone. I'm Dr. Amy Oxentenko, professor of Medicine and vice dean of Practice at Mayo Clinic in Rochester, Minnesota, and currently serving as ACG president. So at ACG 2024, I gave a talk on celiac disease, what's new and what's on the horizon.

So there's so much that we already know about celiac disease. I think we have great tools to help us make the diagnoses with very highly sensitive, highly specific serology. We know what we should be looking for on histologic biopsies to help with that confirmation. We also know what are some of the risk factors for celiac disease. We know that you have to be genetically predisposed to celiac disease. We know that you need to be consuming gluten. but there's also this big huge black box of other things that contribute to risks that we're still sorting out. We know some of those risk factors could be related to global variation and prevalence based on where in the world you live. It could be based on the latitude that you live in based on past studies. The other thing we know is that it can present differently based on if you're an adult versus a child And some of those variations are really important to appreciate depending on the practice that you have and the patients that you see so that you think about the diagnoses in more patients.

So I think what's important is when we think about, well, what's on the horizon for celiac disease. And I know so many people ask each year is, is there a new cure for celiac disease? Is there a pill that I can take so that I don't have to follow a gluten-free diet? And I really look forward to the day where a talk will have something other than the gluten-free diet as the standard of care and the only first-line therapy for celiac disease. We're not there yet, but I'm convinced that we're getting there and I'm convinced that we're closer than we have ever been before.

And in fact, a statement that I made at ACG, which I still hold on to, is that I think we will make more strides and advances in the next 5 years in patients with celiac disease than we've made in the last 50 years. And why do I say that? Well, we understand the physiology so well in patients with celiac disease and what puts them at risk, what allows their immune system to be triggered. And so many of the pharmacologic targets are really looking at those sorts of pieces of the physiology. Anything from how we block gluten in terms of getting through the bowel wall and triggering the immune system. But what I think the heart of the future therapeutics will be is how we alter how our immune system reacts to stimuli. We've seen so many advances of this in terms of let's say the hematologic world and CAR-T therapy and how we can offer CAR-T therapy for a number of different things within the hematologic malignancy space, but now we're also seeing in other benign conditions, other autoimmune and rheumatologic conditions. So I have no doubt that celiac disease will be one of those in line that as we learn more about our immune system, and we know a lot related to that in the world of celiac disease, how we can make it react differently to things that we know can trigger it. So  I think that's going to be probably where the heart of the therapeutics in celiac disease will be.

Will it ever fully replace a gluten -free diet? I don't know. I think it very well could. I think for right now, all of those therapies that are in clinical trials, really in my mind right now would serve as an adjunct once they'd be commercially available. But I think for now, the goal on the horizon is, could we have something that could allow those patients with celiac disease to eat what they would like but we're not there yet and what I think is such an interesting sort of fascination to think about is we have our patients with inflammatory bowel disease for which we have many and evolving therapeutics to offer them to help manage their disease, yet so many of those patients ask for a dietary treatment for their condition. On the other hand we have patients with celiac disease who have dietary treatment as the treatment and the only treatment of choice, yet they're seeking a drug therapy to help avoid the dietary treatment. So it shows again that people are looking for something to ease the burden of their disease and we know that's significant in patients with celiac disease. The impact on quality of life is truly significant and on par with other chronic conditions that we know of that have significant quality of life impact.

And so there is a future. I think we're close. I think we still have a ways to go, but I think, again, looking at gluten degradation, the bioavailability and the half-life of gluten, how we can affect intestinal permeability, how we can affect cytokine activity, all of those are important, but I think the root of the matter is how we can impact our immune response to gluten that's ingested in those patients who are particularly susceptible. So I think that's where we're headed, and I'm excited to see what the future brings for celiac disease management going forward.