Q&A: Dupilumab improves eosinophilic esophagitis outcomes for up to 52 weeks

Key takeaways:

• Other eosinophilic esophagitis treatments may have painful side effects.
• Dupilumab improved histologic, symptomatic and endoscopic outcomes in adolescents and adults.
• Research is ongoing in pediatric patients.

Adolescents and adults experienced sustained improvements in eosinophilic esophagitis outcomes with dupilumab for up to 52 weeks, according to research presented at Digestive Disease Week 2023 in Chicago.

Patients experienced better histologic, symptomatic and endoscopic outcomes during Part C of the phase 3 LIBERTY-EoE-TREET study despite any previous swallowed topical corticosteroid (STC) use or inadequate response, intolerance or contraindications for STCs.

Further, Parts A and B of the study showed that dupilumab (Dupixent, Sanofi/Regeneron) was effective in improving eosinophilic esophagitis in adolescents and adults whether or not they had a history of dilation.

STCs are one option for EoE, the researchers said, but they are associated with side effects, and some patients may not respond. Additionally, dilation does not modulate underlying inflammation. Dilation status may impact interpretation of clinical trial data as well.

Healio spoke with Albert J. (Arjan) Bredenoord, MD, PhD, consultant gastroenterologist at the Academic Medical Center Amsterdam and professor of neurogastroenterology and motility at the University of Amsterdam, to find out more about these results.

Healio: What impact does EoE have on adolescents and adults and their quality of life?

Albert J. (Arjan) Bredenoord

Bredenoord: EoE is a chronic and progressive inflammatory disease that damages the esophagus and prevents it from working properly. For some people with the disease, swallowing even small amounts of food can be an uncomfortable and worrisome choking experience. The disease is often poorly understood, and people with EoE are often left to contend with the frustration and anxiety of a constantly evolving list of foods to avoid, a poor quality of life and a higher risk for depression. In cases where EoE causes the esophagus to narrow, forced and potentially painful dilation (physical expansion) of the esophagus may be needed.

Healio: What are the current treatments for EoE in these age groups, and how does dupilumab improve on these treatments?

Bredenoord: Dupilumab is the first and only medicine formally approved to treat EoE in adults and children aged 12 and older in the U.S. It is a monoclonal antibody and blocks signal molecules that are drivers of the type 2 inflammation underlying the disease, and so it stops that inflammation.

Sometimes other medicines are prescribed for EoE, such as proton pump inhibitors (PPIs) and STCs, but these are not formally approved for this use in the U.S.

There are also food elimination diets being used as treatment for EoE. The objective of these diets is to avoid foods that cause the inflammation, but it is a challenge to find out which foods are problematic and for some patients to adhere to the recommended diet.

Additionally, dilation of the esophagus to address narrowing is often painful and does not modulate the underlying inflammation.

Healio: How do these latest results from LIBERTY-EoE-TREET build upon previously released data from the study?

Bredenoord: Several abstracts in this patient population and specifically building on the LIBERTY-EoE-TREET study were presented at Digestive Disease Week 2023.

One late-breaking abstract that built upon previously released data examined the effect of long-term use up to 52 weeks of dupilumab on histologic, symptomatic and endoscopic aspects of EoE in PPI-refractory patients. This new analysis focused on Part C of the study, in which eligible patients who completed Part B for 24 weeks entered Part C and received dupilumab 300 mg dosed weekly for 28 weeks. Patients were categorized based on prior STC use and response to STC at the screening visit, and the findings showed that dupilumab was efficacious regardless of STC use. Patients treated with dupilumab showed sustained improvements in histologic, symptomatic and endoscopic aspects of EoE up to 52 weeks, regardless of prior STC use or inadequate response, intolerance or contraindication to STCs.

In addition, findings from a pre-specified analysis to assess the efficacy of dupilumab vs. placebo at 24 weeks in patients from Parts A and B of LIBERTY-EoE-TREET with and without prior history of esophageal dilation were presented. The analysis showed that dupilumab improved outcomes vs. placebo regardless of prior esophageal dilation status. So even the severe patients that had dilations before had good response to treatment with dupilumab.

Healio: How can these findings help doctors improve care?

Bredenoord: The data shows that dupilumab works well for all types of PPI-refractory EoE patients. That’s important information for doctors.

Healio: What is the next step in this research?

Bredenoord: We are committed to continued evaluation of dupilumab in the EoE patient population, including in young children aged 1 to 11 years through a pivotal trial. Currently, there are no approved treatments for EoE in children aged younger than 12 years. Like adults and children aged 12 years and older, EoE can impact a younger child’s ability to eat, which is critical in early childhood when healthy weight gain is vital to long-term health and development. The ongoing three-part phase 3 EoE KIDS trial is evaluating the efficacy, safety and tolerability of dupilumab vs. placebo in pediatric patients aged 1 to 11 years with active EoE up to 16 weeks. Findings were reported at Digestive Disease Week from Part A of the study, which met its primary endpoint of histologic disease remission at 16 weeks with dupilumab.

References:

• Bredenoord A, et al. 467. Presented at: Digestive Disease Week 2023; May 6-9, 2023; Chicago.
• Bredenoord A, et al. 913f. Presented at: Digestive Disease Week 2023; May 6-9, 2023; Chicago.