Impact of dupilumab on esophageal remodeling in EoE: 24-week REMODEL findings

touchIMMUNOLOGY coverage of DDW 2026

Could you describe the progression of EoE if left untreated?

We generally think that EoE is a progressive condition in most people and it moves from an inflammatory condition to a fibrostenotic condition. Over time allergic inflammation drives a profibrotic response resulting in strictures, which are focal constrictions of the esophagus, or diffuse narrowing of the esophagus. We know that this happens because of studies that have followed patients over time and retrospective studies.

In general, the longer patients have symptoms, the higher chance they have of developing esophageal strictures or needing dilation. For example, if a patient has symptoms for only a few years, maybe 15–20% will have strictures, whereas if they have symptoms for more than 20 years, maybe 80% will.

It is not an inexorable progression in everybody and there are some people who present with strictures and fibrosis after a short period and others who never get it. But in general, people will tend to progress over time if they are not effectively treated. I should clarify that the consequences of fibrostenotic progression are not limited to symptoms like food sticking and dysphagia. They also include complications such as food impactions requiring emergency removal, as well as the need for esophageal dilation, which is the standard therapy for established strictures.

Where does dupilumab fit in the treatment paradigm for EoE, and what was the rationale for the phase 4 REMODEL trial?

The new guidelines from the American College of Gastroenterology generally position the biologic dupilumab as a step-up therapy for patients who have not responded to a first-line treatment, such as proton pump inhibitors (PPIs) and/or topical steroids. Generally, dupilumab is used for the more difficult to treat patients, but the guidelines do consider its use earlier in the disease course for patients who might have other atopic conditions that also merit dupilumab use.

We know from clinical trial data and real-world data that dupilumab is effective at improving symptoms and biopsies in terms of histologic response. What we don’t know is whether dupilumab can resolve fibrostenotic changes and esophageal remodeling over time, and this really formed the basis for the REMODEL study. In other words, we were looking at the changes that lead to scar tissue and fibrosis.

In the phase 2 study of dupilumab, a small subset of patients had their esophageal diameters measured, using a technique called EndoFlip. This demonstrated an improvement in the size of the esophagus over the study, but we couldn’t say definitively whether this was causal, as this was an exploratory outcome and involved such a small number of people.

Improvement in esophageal diameter has been associated with other successful treatments, such as PPIs, topical steroids and dietary elimination, but it has not been rigorously evaluated in clinical trials. A treatment that could help to resolve or reverse fibrosis and fibrostenosis would be really useful in the field.

Could you describe the design and endpoints of the study?

The REMODEL study was a double-blind, placebo-controlled study, where patients were randomized 2:1 to receive either dupilumab 300 mg weekly or placebo. Patients were ≥18 years of age, and they had to have active EoE, symptoms of dysphagia, and to have previously been non-responsive to PPIs. These are essentially the same inclusion criteria as the phase 3 study that led to approval in adolescents and adults.

After the randomization, patients were treated for 24 weeks and primary outcomes were assessed. After that, patients could continue into open-label treatment, which is ongoing and has a duration of 2 years. The data that we are presenting are the results of the 24-week, double-blind phase and the longer-term data are still being collected.

The primary outcome for the study was esophageal diameter, which was measured using EndoFlip, which I mentioned briefly before, and by looking at a metric called the distensibility plateau. We also looked at other outcomes, such as histologic response and eosinophil counts, endoscopic severity as measured by the EoE Endoscopic Reference Score (EREFS), and histologic severity as measured by the EoE Histologic Scoring System (HSS). We monitored for safety as well.

For those who don’t know, the EndoFlip device is a balloon-based catheter that we use during an endoscopy while the patient is asleep, and we put the balloon into the esophagus and inflate it. This test has been around for a number of years and has mostly been used for esophageal motility problems. When the balloon is inflated, the normal response of the esophagus is to squeeze to push the balloon into the stomach, a process called secondary peristalsis, and this happens even when people are asleep during the endoscopy.

The balloon also allows us to measure how stiff the esophagus is, known as compliance, and because of the catheter’s design, it can measure the diameter of the esophagus as well. We inflate the balloon with increasing increments of fluid, and once the balloon reaches the esophageal wall, it can no longer expand. As more volume is added, the pressure inside the balloon rises. That increase in pressure indicates that the balloon has reached the esophageal diameter, allowing us to identify the narrowest diameter of the esophagus, which was the primary measure.

How well were the primary and secondary endpoints met?

At week 24, all of the outcomes were met. For the primary outcome, we found that dupilumab significantly increased the esophageal diameter compared to placebo, with about a 1.3 mm difference over those 24 weeks. In other words, patients on dupilumab had an improvement in esophageal size. While that may not sound like a large change, it can be comparable to what might be achieved in a single dilation session, depending on the patient.

In a sub-analysis, we looked at how narrow the esophagus was at baseline. We typically use a cut-off of 17 mm, above which patients are not felt to have significant fibrostenosis, and below that is where we consider the esophagus to be narrowed or strictured. In the group below 17 mm, there was a larger increase in diameter, about 2.3 mm over placebo at 24 weeks. Patients already above 17 mm had less room for improvement, whereas those with smaller diameters showed the greatest benefit. Notably, the inclusion criteria did not require a minimum esophageal size, as long as a standard endoscope (which is about 10mm or less) could pass.

In terms of the other responses, we also saw significant improvement in endoscopic severity, measured by EREFS compared to placebo, similar to what was seen in the phase 3 trial. Histologic severity also improved, not just in eosinophil count, but across a range of biopsy features.

How will these findings impact clinical practice?

I think the findings from the REMODEL study will impact practice in a few ways. We already know from the phase 3 trials that dupilumab improves histologic response and symptoms, but these results add more context. First, they provide insight into the mechanism of symptom improvement, showing that it is not just due to reduced inflammation, but also to increased esophageal diameter. We now have a clearer sense of the magnitude of that effect. In patients who start with a distensibility plateau or a diameter below 17 mm, the improvement is about 2.3 mm compared to placebo, which approaches what might be achieved with one or two dilation sessions.

In practice, this may mean that after starting this medication, it could be reasonable to defer dilation in patients with mild to moderate strictures and instead monitor them over time. It is also important to note that these are 24-week data. Reversal of fibrostenosis is generally slower than reversal of inflammation, so as follow-up continues, it will be interesting to see whether esophageal diameter continues to improve. The hypothesis is that it will, and if so, this would suggest the potential to slow or even reverse disease progression in EoE, which would be an exciting development if confirmed.