Q&A: Dupilumab may help patients with eosinophilic esophagitis return to ‘normal’ diet

Researchers at Children’s Hospital of Philadelphia have recently been gifted $2 million to begin conducting a clinical trial studying the effects of dupilumab on patients with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic allergy inflammatory disease of the esophagus, often triggered by one or more food allergies, such as milk, eggs, wheat, soy, beef, chicken, potato and corn. Food avoidance is one of the most common treatments of EoE, and patients are often excluded from clinical trials for oral therapy due to the potential severity of symptoms after ingesting their treatment foods.

This study, however, aims to use dupilumab (Dupixent; Sanofi Genzyme, Regeneron) to introduce treatment foods back into the patients’ diets.

In an interview with Healio, Jonathan Spergel, MD, PhD, chief of the allergy program at Children’s Hospital of Philadelphia, discussed the symptoms of EoE, its effect on quality of life and what this new study aims to find.

Healio: What is the prevalence of EoE and how do the symptoms affect quality of life for patients?

Spergel: Our current estimates are that EoE affects about one in 1,000 to one in 2,000 people. It's a rare/uncommon disease, so it's not as prevalent as asthma, eczema or seasonal allergies, but it’s much more common than the rare immunodeficiencies.

Jonathan Spergel

EoE is a different type of food allergy that affects your esophagus; so, it’s not like a food allergy where you eat a food and get hives. Rather, when you eat a food, your esophagus gets irritated and swollen. Babies and young children present with reflux, abdominal pain and vomiting, which is a real problem. In adults or teenagers, EoE presents as dysphagia or food impaction. The esophagus really doesn't work as well, so food gets stuck going down.

EoE really affects patients’ quality of life, and people who have untreated EoE end up with compensation mechanisms — they'll eat slowly, drink lots of water, avoid thick foods, and are careful with foods such as breads and steaks. It has a dramatic effect on the quality of life for patients.

Healio: Why has EoE been particularly challenging to study in the past?

Spergel: One of the problems is that EoE is a newer disease. It really has only been described in the last 20 years, so we didn't have a lot of knowledge beforehand. Although the symptoms of EoE affect quality of life, they can be delayed, which has been another of the challenges we've had to studying it. Also, it's not as common as other diseases, so we don't have a huge patient population for treating the disease.

Healio: What is the rationale for studying dupilumab in patients with EoE?

Spergel: It comes from two things. We know that this is an allergic disease, so it involves the classical allergic pathway — IL-4, IL-5 and IL-13 — that drives the inflammation. If you measure those levels in human biopsies, particularly IL-13, it really drives disease. If you gave mice extra IL-5 or IL-13, the mice get more EoE. These are key molecules to drive that allergic inflammation, leading to more eosinophils going to the tissue, causing tissue damage and disease.

Dupilumab, which is now approved for several atopic conditions, such as asthma and atopic dermatitis, has been very successful in turning down that allergic inflammation. There have been phase 2 clinical trials, as well as phase 3 clinical trials, in EoE that have shown a fair amount of success. The company has finished their big phase 3 trial, and they have released results that show it works. But the patients in the trial were directed to not change their habits — they only can eat what they were eating, and they can't reduce or change medications. What patients with EoE really want is to be on a drug where they’re able to eat the foods they had been avoiding, which is what this study is really going to evaluate. We’re seeking to answer a key clinical question that patients care about, which is, ‘Can I, now that I’m on this drug, eat this food?’

Healio: How will you conduct this study?

Spergel: Once we enroll patients, we’ll make sure they are true responders to dupilumab. We expect about two-thirds of patients will respond based on the previous clinical trials, but we don't know until we do the study. Then we will do endoscopies and biopsies to find out which patients have active disease. An upper endoscopy is standard of care to diagnose the disease.

The next step is to add foods into the patient’s diet that they have been avoiding and do another biopsy. We’re going to start with a small amount of food, and then we slowly try to increase it. The patient will add one food for a couple months, and then they can either do a second food or more foods as time goes along.

Healio: What do you hope your study will find and what do you think the implications of the findings will be?

Spergel: The goal is to determine whether this drug can improve the quality of life of patients with EoE so that they feel well and can eat a more normal diet. I always think about this over the holiday period. It’s like, can I eat my Thanksgiving dinner with the gravy, have that pie at the end and really not have that food getting stuck? Can I have a normal Thanksgiving? That is really the goal, to find that we can do it. We’re very excited to conduct this study, and we have to really thank our patient donors because it was a question that they raised.