We have a little bit of time for questions, yeah. Have you ever seen evidence where people outgrow EOE? So there isn't clinical evidence to show that people will just outgrow it necessarily like kind of asthma. We do, I do see that patients sometimes go in and out of being inflamed even if they're not treated sometimes. There are a lot of patients that I see I continue to do endoscopy periodically over time and some patients even if they get off therapy they just remain in remission for a period of time but then a lot, most of them eventually will flare back up. So you know I don't think we know, I don't think there's really evidence to show that but you know we still need to learn more about the disease. So everything is in our body for a reason right to help us with homeostasis, IL-4, IL-5, IL-13, do they have any good function in the body? Absolutely, so yeah because there are certain things that you want to mount an immune response to, things that might cause harm to the body, you want your immune system to be able to fight them, infections and other things. So there all these have functions, essential functions of their own as part of the immune system. So it's just when they're overactive, when they're overactive to things that you normally should be able to tolerate, that's when it becomes a problem. Are there certain infections they're geared for or just in general? In general, in general, it can be infections or other potential harmful triggers. So it's really the dysregulation of this process that's become the problem. When it's being activated by normal things that we should not be reacting to, that's when it's the issue. Yeah, go ahead. Just a quick question, from a treatment approach, you have that team approach, what's it look like, your interactions with allergy? How does that work when you have GI and allergy, like at the Brigham, what would that look like? Yeah, that's a very good question because as you probably know, a lot of the allergists also see a lot of EOE patients. This is sort of a population that's shared by two specialties. And because allergen being a trigger is such a big component of this, oftentimes having the allergist to help us, especially in the more complicated patients, to avoid certain allergens and treat the underlying allergy is helpful. Having said that, there have been a lot of studies looking at, should we routinely send these patients for allergy testing? Should we routinely do food allergy testing? And what the data has found is that they're not terribly useful in guiding therapy. So for example, for diet treatment, is it useful to do food allergy testing for everybody before we start that? It turns out they're not very predictive. So we don't currently routinely send every patient for allergy, just allergy testing if they don't already report potential symptoms for it. But there are certainly populations, especially more complicated patients, where it might be useful. Yeah. Go ahead. I've heard there's can be quite a bit of variance on EOEs, on what a patient is doing. Biopsy is done from physicians. Can you give a little more background regarding that? You mean in terms of what they've been eating and when they ate their meal, especially when the biopsy was done? And when the biopsy was taken? Yeah. Yeah. So I don't think there's much study in terms of if you were to eat something right away and we do the endoscopy immediately and get biopsies, does that make a difference compared to not timing it? Because most of the time when we do endoscopy, patients have to be not eating for a number of hours before anyway. But this is likely not just one meal. It will trigger something and will trigger all the changes you see on the endoscopy. It likely is a repeated insult over time. So that's why when we make these diagnoses, when we follow up on therapy, we want to give it enough time. For example, we put something on treatment, usually we will wait about 8 to 12 weeks before we do a biopsy to see if they responded or not. Because you need to give it time to change. And it's likely not just a one-time thing. Yeah. I was just wondering if that's what the theory is that the prevalence is down after 40? I don't think we completely know, but I think the thought is that patients oftentimes has symptoms pretty early on. So most of the time, by the time they get to their 40s, they have already been diagnosed. The most patients have already been diagnosed. So I think this highlights the fact that most patients who have this, have them early on in life. You're not going to, it's less likely you would develop it if you never had issues with allergy or swallowing or anything. Yeah, go ahead. So you mentioned that once patients get to the fibrotic stage that most likely they won't respond to therapies as well. Is it widely accepted in the community that it's irreversible damage at that point? Yes. For the fibrosis, so the definition of these fibrotic changes is that they are scar tissues essentially. Okay. Fibrosis is essentially a scar. Kind of like cirrhosis, it's fibrosis of the liver. It's basically scarring of the liver. So at that point, at least with current treatment, there's no current therapy that can reverse these scar tissues. Yeah, go ahead. You stated that you'll sometimes flare up seasonally. Does that mean that you'll only give treatment seasonally as well, or will you keep them on therapy throughout the entire year? So the current guideline is that you should be on maintenance therapy. You're right, there are definitely patients that more likely flare up symptomatically during certain seasons, or if they know they're going to be exposed to certain things. But again, because these changes are likely chronic changes from repeated exposures over time, the current recommendation is everyone should be on maintenance therapy and not just on and off. Now, that might be something that, depending on your therapy that comes up, that kind of guidelines might change if a new study comes out that says that actually it might be safe, but according to current, at least the current guidelines, you shouldn't just kind of start and stop. Yeah, go ahead. For a current patient, my protocols with my physicians are they're waiting for the treatment guidelines to be updated on when to use Dupixent. Some have said I expect them in a month, some have said probably not for a year. I'm just curious if you have any thoughts or opinions on that. You mean like if they have not been responding, or... Just where they... Where they would fit into the... Yes. Yeah, so it's not in a guideline. I think the main thing that's been looked at in the populations and studies may need a refractory patients to existing therapy. But having said that, it is the only FDA approved therapy. So it's also a therapy that's already in use for other conditions. So I think ultimately, this most likely will become one of the treatment options along the side of steroid diet and other things, as long as they get covered. I think that ultimately will be a big determining factor. But you're right, it's not currently in the guidelines just yet. But there's no reason to think that they can't be one of the options, equal options. Can you help clarify for me, like strictures versus fibro... Yeah. Fibros... Stenotic changes. Yeah. I think that's where I'm getting a little chucked up. Yeah, we're using these terms very interchangeably, but they are actually meaning a very similar thing. Fibrosis is what we see oftentimes under the biopsies, is these changes of basically scar tissue deposition on the biopsy slide. When you have a lot of fibrosis, that's when you start having these strictures that form, which is the narrowing. And when it's narrow, they'll often say that something is stenose, which basically mean that the lumen, the diameter is smaller. So we're trying to talk about the same thing, but the fibrosis is the underlying process of these scar tissues happening. Stricture is often what we see on endoscopy described as having a stricture, which is those little narrowing that we see. And the stenosis is really a description of the size, when something is stenose, it's narrowed. But you could not have a stricture then without fibrosis, is that what you mean? Essentially. Okay. So that comes from fibrosis. Now, EOE is one condition where that can happen, but there are other type of stricture that we see in esophageal diseases. One of them I think earlier that was talked about was reflux. Reflux can cause esophagitis, and that can also lead to stricture called peptic stricture. So there are other different types as well. So these terms are having stricture, having stenosis are not specific to EOE. You can see that in other conditions, but it is just one consequence, a late stage consequence of having EOE. Yeah. Go ahead. So I think you talked about that already touching base a little bit, but when you start somebody on a PPI and or a swallowed steroid, what's that look like in terms of following that patient for a response? How quickly do you see them? How do you evaluate response? Sure. I don't want to steal Rishi's thunder. I'm sure he's going to go into a little more details of it, but I think the short answer is that I think the important thing is that you always, the only way to know if someone responded is by biopsy. So everyone, when I treat them, I always biopsy them. If I change a treatment, I always biopsy them after. Is there a timeframe? I usually wait eight to 12 weeks. That's pretty standard, I think. I would just piggyback on the previous question. In terms of long-term management of patients with EOE, what is the thought process around future biopsies, assuming you haven't changed therapy, and assuming that patient isn't necessarily saying, hey, I'm having more symptoms, maybe they're not identifying, where do you think that's going? Yeah. You know? I think you're asking the million-dollar question there, because we don't have that in our guideline right now. Right. And if you ask 10 different gastroenterologists, or even esophagologists, they might give you 10 different answers to what they do. I can tell you what I do. I usually actually do surveillance endoscopy with biopsies, usually every one to two years at least initially. And if they remain well and there's no, and things remain in control, I might space that out later. But I have been, and I am still doing the surveillance endoscopy, partly because one of the things we know is that symptoms and histology on biopsies don't match. A lot of times patients will have no symptoms, and you biopsy them, you might start seeing eosinophils. And you want to catch them early if they start having inflammation before they develop symptoms, so that you can start treating them. And so that's one of the reasons why I've been doing surveillance. And I've definitely caught a few patients where I start seeing inflammation, and I see them back in clinic, I say, look, this is what it shows, I don't know what happened. And they're like, oh, yeah, now that you say that, I've been noticing a little bit of symptom recently. Or they might say like, oh, one patient of mine actually was that he just had a baby, and they're using a certain type of formula for the baby, and it turned out that he might actually have an allergic reaction to that. And later on, that all went away, and he went back into remission when he stopped feeding baby with that formula. So there are many different reasons that can be causing those, and sometimes it will be hard to catch just by basing on symptoms alone. If a patient expresses a change in symptoms, they may not biopsy for indefinitely. And what is the risk of that for the patient? Yeah, and honestly, we don't completely know. And that's why we can't say that that's the wrong approach either, according to the current guideline, because we just don't have enough data to say that. I think anecdotally, I've definitely identified patients that flare up, even though there's no change in therapy. But how often there is, is there a specific therapy that happens more in? We don't completely know. Thank you.

eosinophilic esophagitis

treatment

immune system response

fibrosis

biopsies