Joy Chang, MD, on Step Therapy for EoE: Part 1

In this video, Dr Joy Chang begins a two-part discussion on using step-up and step-down therapy in the treatment of eosinophilic esophagitis based on her presentation at the ACG scientific meeting.

Joy Weiling Chang, MD, is an assistant professor of medicine in the Division of Gastroenterology at the University of Michigan in Ann Arbor, Michigan, where she specializes in diseases of the esophagus.

Clinical Practice Highlights

• Treatment options: Multiple first-line options are supported for the treatment of eosinophilic esophagitis (EoE), including proton pump inhibitors (PPIs), topical steroids, dietary elimination, and the biologic dupilumab, with shared decision-making based on EoE severity and patient preference, as no head-to-head trials compare medications versus diet.
• Drug class: Proton pump inhibitors (PPIs). In prospective and retrospective studies and recent systematic reviews/meta-analyses, PPIs induce histologic remission in ~50% and clinical response in ~60% of patients with EoE, with similar efficacy in adult and pediatric populations; PPIs are convenient, low cost, and generally safe, supporting a step-up approach starting with PPIs.
• Dietary therapy and escalation strategies. Dietary elimination targets food-antigen–driven inflammation; efficacy varies by diet and can be first line for patients preferring nonpharmacologic care. The traditional top-down 6-food elimination diet is well studied, while newer randomized trials and ACG 2025 guidelines support step-up, less restrictive approaches (e.g., eliminating dairy or dairy plus wheat first), reserving broader elimination or biologics for harder-to-treat cases.

TRANSCRIPT:

Hi, everyone. I'm Joy Chang. I'm an assistant professor of medicine at the University of Michigan here in Ann Arbor, where I specialize in esophageal diseases and specifically eosinophilic GI disorders such as eosinophilic esophagitis. At the recent American College of Gastroenterology 2025 post-grad course in Phoenix, Arizona, I presented about using step-up versus top-down approaches to treating eosinophil esophagitis or EoE.

Now, it's really an exciting time to talk about EOE since we're learning so much more about it now. And we have so many new available treatments in the last couple of years, but sometimes having all those choices and options can be more challenging because what do you do first? What do you do next? So during the presentation, we looked at the recently published ACG guidelines from 2025 to see that patients have various options for therapies, including proton pump inhibitors, topical steroids, diet elimination, and then our new biologic dupilumab.

And interestingly, if you look back at some of the evidence, we know that prospective and retrospective studies show that diet and medications are effective in inducing and maintaining long-term disease remission. And so it reduces the risk of food impactions, improving health-related quality of life. These guidelines also support shared decision-making in determining what's the best therapy first line with consideration of the severity of EoE.

Now, if we look to our literature though, we'll see that there are actually no studies comparing the efficacy of medications versus diet. There's only a few studies comparing medications against each other. And so there's a lack of head-to-head comparative trials telling us what is best or really what should be first line. And so we've heard about this concept of step-up versus top-down treatment, certainly within GI and a lot of practice in inflammatory bowel disease, but this idea also exists in other disease states, pulmonary allergies and whatnot.

And so this idea of stepping up is essentially starting with mild drugs and then adding stronger medications if these fail and then slowly going up in intensity, versus top down, which is essentially starting with the most potent medications like biologics from the start.

So what does that look like in EoE? For stepping up in EoE, that kind of looks like starting with proton pump inhibitors, maybe going to topical CRAs or a dietary therapy, and then using or saving biologics for hard-to-treat cases. And then conversely, a top-down approach would start with biologics upfront, for example. And so if we kind of look at what that looks like in EoE, starting out with a step-up approach, starting with proton pump inhibitors, the reasons behind doing this and starting with a proton pump inhibitors are many. We know that PPIs or proton pump inhibitors are effective in controlling EoE and about 40 to 50% of people with EoE.

And we can see from several recent systematic reviews and meta-analysis that proton pump inhibitors lead to histologic remission, about 50%, clinical response at about 60%, and no huge differences between adult and pediatric populations. Now, for the gastroenenterologists, we have had proton pump inhibitors around for some time and we experienced how convenient it is to use it. Certainly people in primary care and allergies, an allergist can also appreciate this too. It's a medication they use once or twice a day. PPIs are generally low cost because they've been around for so long, and pretty safe as well. So using reaching for proton pump inhibitors first, not a bad bet. Now, if we step up from proton pump inhibitors, our choices for medications include topical steroids, including the recently FDA-approved budesonide oral suspension, as well as our off-label preparations of topical steroids like budesonide slurry or swallowed fluticasone.  And then finally we have the biologic dupilumab as well.

Now, what about dietary therapies? The idea behind dietary therapy is this rationale that the eosinophilic predominant inflammation that is characterized by EoE is precipitated by food antigens. So the goal of dietary therapy is to induce disease remission by removing food allergens and then systematically add foods back to identify which foods are safe foods versus trigger foods. So dietary therapy can be another great option. And for some patients who prefer a nonmedication, nonpharmacologic alternative can be really great.

Now, the estimated efficacy of dietary therapy can really depend on the diet, but again, diets can be first line as well. So patients don't always have to do PPIs or proton pump inhibitors first. Sometimes that's guided by the preference of patients. A patient who wants to start treating their disease without using medication, diet can work. And for a lot of patients, the dietary therapy kind of treats that root cause by eliminating food triggers.

Now, if we think about things that are step up or top down, diets alone can be step up or top down. And during the presentation, we talked about what that looks like. The original kind of original recipe for the dietary therapy was called 6-food elimination diet. So empirically removing dairy or animal milk, wheat, soy, eggs, nuts, tree nuts, and shellfish and fin fish. Now, that's a lot of foods. And so that's more so your top down, so you're taking away lots of things. And then a step-up approach kind of takes the approach of over the years, we've now come to appreciate that dairy or animal milk and we are the most common EoE triggers. So a step-up approach might look like starting by eliminating those alone and seeing if you can isolate the food trigger that way. And if not, then progressively taking things away.

Now I mentioned the 6-food elimination diet is the most well studied, kind of the original recipe, but there's been some recent work, including a couple randomized controlled trials and systematic reason and analysis of the dietary kind of studies showing that it might be a decent idea to start with less restrictive diet. So essentially eliminating most common triggers or dairy and wheat first, especially if taking away one food is going to be a lot easier than taking away six. And so the new ACG guidelines also are in support of that, starting with a less restrictive diet if a patient wants to do dietary therapy.