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GI UpdatesTwo recent studies show dupilumab improves eosinophilic esophagitis symptoms and pathology for adolescents and young adults – offering new hope for younger children with EoE.
A recent clinical trial by an international group of researchers — including Children’s Hospital of Philadelphia (CHOP) — found that a weekly dose of dupilumab, a human monoclonal antibody, led to a reduction of symptoms and tissue improvement in adolescents and young adults with eosinophilic esophagitis (EoE). The study analyzed data from two phase III clinical trials and findings were recently published in the New England Journal of Medicine.1
Traditional treatments for EoE include food elimination diets, topical glucocorticoids, proton-pump inhibitors and esophageal dilation. However, about a third of patients do not respond to these first-line treatments; and some patients experience negative side effects with them.
Researchers began investigating dupilumab as a potential treatment for EoE after growing evidence suggested type 2 (T2) cytokines play a key role in EoE. Dupilumab blocks interleukin-4 and interleukin-13 — two key drivers of inflammation in patients with EoE. The subcutaneous medication is approved to treat several inflammatory diseases including asthma, atopic dermatitis and nasal polyps. A phase II trial involving adults with active EoE showed a weekly dose of dupilumab (300 mg) reduced symptoms and improved esophageal tissue.
In the recent three-part, phase III trial, we assessed the efficacy and safety of dupilumab in three groups of adolescents and young adults (aged 12 and older):
We found the 300 mg dose of dupilumab given weekly reduced symptoms and improved histologic outcomes in patients, while the same dose every two weeks improved histologic outcomes in patients but did not improve symptoms. Findings were reported with a 95% confidence interval.
Trial results provide hope to patients and families who’ve historically had limited options to treat EoE and demonstrate dupilumab is a viable treatment option for patients with EoE. The study provides further evidence that dupilumab reduces symptoms of EoE in adolescent and adult patients and targets the root cause of the disease.
At Children’s Hospital of Philadelphia, we’ve been using dupilumab to treat EoE for about 5 years — in some cases after traditional treatments have failed, and in others for compassionate use or to offer patients expanded treatment options.
EoE can be a challenging disease for youth — and their families — who must be careful about everything they eat. To avoid excessive inflammation in their esophagus, patients must avoid their “trigger food,” which can be difficult when the most likely trigger is one of the four most common foods — milk, eggs, wheat or soy.
Dupilumab was originally FDA-approved to treat patients with atopic dermatitis, asthma and nasal polyps, but we discovered many of our EoE patients with these comorbid conditions demonstrated improved results of EoE symptoms while on the medication. We collaborated with Rady Children’s Hospital in San Diego, CA, on a retrospective chart review in 2020-21 of all our pediatric patients who were prescribed dupilumab for asthma, atopic dermatitis or nasal polyps with a concomitant clinical diagnosis of EoE.
After collecting histology, symptom scores, medications and diet information, we evaluated patient response to dupilumab. We found dupilumab therapy induced symptomatic and histologic remission of EoE and reduced the need for traditional EoE treatments in most patients. Our findings were published in the Annals of Allergy, Asthma & Immunology.2
Slides of patient-derived organoids
CHOP’s Center for Pediatric Eosinophilic Disorders was one of the first multidisciplinary pediatric programs in the United States created to diagnose and treat children with EoE and other eosinophilic disorders. When we founded it 20 years ago, we saw fewer than 100 patients a year; today, we treat more than 700 unique patients a year, and since we started, we’ve treated more than 3,500 patients with EoE — one of the largest pediatric clinical populations in the world.
Our clinical team includes specialists from gastroenterology, allergy, nutrition, and pathology, as well as a dedicated nutritionist, psychologist, and feeding team focused on the specific needs of EoE patients. We treat patients holistically and offer:
Treatment for EoE has evolved as we’ve learned more about the disease and its triggers. Some recent highlights in testing, research and treatment include:
In the past 10 years, we’ve uncovered many mysteries surrounding EoE and have developed consensus on how best to diagnose it. We’re still investigating alternative and less invasive treatments that will remove the trigger to esophageal inflammation or block it with medication or by other means.
We just finished a new clinical study at CHOP to determine if dupilumab could be used in younger children with EoE. We are now investigating to see if dupilumab can allow patients to expand their diet and add their EoE trigger foods to their diet when their inflammation is controlled by dupilumab. We anticipate an increasing number of systemic therapies may be developed that offer the opportunity for concurrent treatment for multiple atopic conditions. Continued evaluation of these medications — and how to maximize their benefits for our patients — is essential.
Jonathan Spergel, MD, PhD, is Director of the Center for Pediatric Eosinophilic Disorders, Chief of the Allergy Program and Director of the Food Allergy Center at Children’s Hospital of Philadelphia.