Joy Chang, MD, on Step Therapy for EoE: Part 2

Dr Joy Chang continues her tutorial on therapy for eosinophilic esophagitis, focusing on step-down therapy that begins with biologic medications.

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:

Eosinophilic Esophagitis (EoE): Step-Up vs Top-Down Therapy

• Eosinophilic esophagitis (EoE) — Dupilumab is the first FDA-approved biologic for EoE, administered as a once-weekly subcutaneous injection. It is a monoclonal antibody targeting the IL-4 receptor alpha, inhibiting IL-4 and IL-13 signaling involved in eosinophil recruitment and fibroblast proliferation. Benefits include efficacy, suitability for patients with adherence challenges, adolescents, and potential benefit in fibrostenotic disease, while limitations include cost, insurance step-therapy requirements, injectable route, and need for long-term maintenance with unknown long-term immune modulation safety in EoE.

• Guideline positioning — American College of Gastroenterology guidelines generally recommend dupilumab as step-up therapy for difficult-to-treat or refractory EoE, including patients who fail proton pump inhibitors, topical steroids, or dietary therapy, or who cannot adhere to daily treatments. Dupilumab may also be considered as first-line (top-down) therapy in selected patients with severe disease or concurrent atopic conditions such as moderate-to-severe asthma or eczema, or those wishing to avoid dietary restriction or topical steroids.

• Clinical practice approach — Step-up therapy commonly begins with proton pump inhibitors, followed by topical steroids (including FDA-approved budesonide oral suspension) or dietary therapy, reserving biologics for severe disease. Top-down strategies may be appropriate for select patients, but treatment choice should be individualized using shared decision-making, incorporating disease severity, comorbid atopic disease, feasibility, patient preferences, and multidisciplinary care, recognizing EoE as a lifelong condition.

TRANSCRIPT:

Now, kind of shifting gears a little bit, we talked about top down. So top down therapy, when we think about what is the top, we usually think about dupilumab, which is our first FDA approved biologic for EoE. Now, dupilumab we've had since 2022, and it's a monoclonal antibody that acts on the IL-4 receptor alpha. It inhibits the IL-4 and IL-13 signaling that's responsible for recruiting eosinophils, fibroblast proliferation. And there's a lot of great things about it, right? It's approved by the FDA. It's effective. It's used as dosed once a week as a subcutaneous injection. And so this might be great for certain populations like adolescents or people who struggle with adherence and maybe remembering to take a medication every single day, and there's potential benefit for fibrostenotic disease and EoE. But there's also some potential downsides, including cost and coverage. So some insurances may require that you fail other treatments first; patient preference, it is an injectable medicine, so maybe patients may not be so interested in that and then kind of needing to use, maintenance use.

So what does that look like in terms of doing injections for a very long time chronically to control the disease and kind of this unknown long-term safety of immune modulation impeachable with EoE? And so we think about several different considerations for using dupilumab and EoE. Do we use it as a step up therapy? Do we save it for people who are failing to thrive on restrictive diets, who've had adverse effects to topical steroids or other medications? They're unable to adhere to daily medications or the dietary therapy or kind of refractory EoE where nothing else is working. Or can we consider it dupilumab as first line so that that top-down approach for patients who have concurrent atopic diseases? So dupilumab is also used for moderate severe asthma and eczema to name a couple. And so could you potentially treat someone who has EoE and asthma at the same time or patients who have a strong preference to avoid dietary therapies or topical steroids?

And so the ACG guidelines kind of provide some suggestion that we advise to use dupilumab as a step-up approach to treat patients, difficult to treat patients, and then considering using it potentially as a first-line therapy to treat EoE and other atopic disorders at the same time. Now, kind of going back to the ACG guidelines, that treatment algorithm, we saw that this nice little word, shared decision-making, is nestled right in the middle of the algorithm. And this idea that we don't have the evidence to show that there's one absolute best treatment. And so what does that look like in terms of making decisions with patients, like letting them guide us with their preferences? And sometimes patients' preferences and values and life situations are very different that makes one treatment easier, harder, and more feasible than the others. And so kind of listening to patients and walking through the feasibility and their self-efficacy around choosing a treatment is also very important and key.

Now, looking at part of the presentation, we also rolled through a case as well of how to think through first treatments, second treatments, what patients really want, and ultimately the take-home points or that step-up therapy can be a very practical strategy. So it starts with proton pump inhibitors because they're effective and safe, they're easy, convenient, and generally low cost. And then if that doesn't work, moving to a medication like a topical steroid, again, these are effective. We have long-term data with this. We have an FDA approved budesonide and oral suspension, which is your topical steroid. But then also for patients who want to do dietary therapy, that stepping up approach works too. Less restrictive diets are okay to try first, and sometimes choosing dietary therapy can be guided by patient preferences. And then finally, saving biologics as a backup plan for severe disease. And so that kind of is an approach to step-up therapy.

Top-down therapy, so essentially early use of medications like biologics like dupilumab or topical steroids, could be suitable for some patients with severe disease or concurrent atopic conditions. But the most important part really is that treatments should be individualized to consider disease severity, patient preferences, other comorbidities like the ATP, and then also shared decision making. So how do we as providers and clinicians take what we know to patients, elicit their preferences and values and find out what will work best because ultimately EoE is a chronic disease? So we're managing this for life. And so it does require a partnership between clinicians and patients and EoE can be a family disease. And so all of that joint decision making can be very instrumental in managing the disease long-term. And sometimes that also includes other multidisciplinary staff such as dietitians, psychologists, allergists, even primary care. So that's my hot take.

Thanks for listening.