Treatment for Eosinophilic Esophagitis Shows Promise
While there is no cure for eosinophilic disorders, a multidisciplinary collaboration of experts at Cincinnati Children's in gastroenterology, pathology, and allergy and immunology, as well as reasearchers, are leading international efforts to find new treatments – and ultimately a cure.
Studies led by Marc E. Rothenberg, MD, PhD, director of the Cincinnati Center for Eosinophilic Disorders (CCED) at Cincinnati Children's, have shown the rate of eosinophilic esophagitis has risen so dramatically in recent years that it may be more prevalent than other inflammatory gastrointestinal disorders, including Crohn's disease.
After discovering the first gene associated with eosinophilic esophagitis, eotaxin-3, researchers have been working to find new treatments for eosinophilic esophagitis. Although current therapies appear to be effective, their long-term use is limited by the need for frequent placement of a gastrostomy tube; inconvenience and cost; and local and systemic side effects.
Some of the newer research breakthroughs are showing positive results in two clinical trials.
Testing Anti–IL-5 as a Therapy
The first trial was an open-label phase I/II safety and efficacy study of anti–IL-5 (mepolizumab) in treating patients with eosinophilic esophagitis. This drug was chosen because it blocks IL-5, an eosinophil growth factor. Dr. Rothenberg has shown that this is effective at blocking the disease in animal models.
Researchers at Cincinnati Children's have recently reported that anti–IL-5 was generally well tolerated. All the patients responded to anti–IL-5 therapy with better clinical outcomes, although to varying degrees. Endoscopic findings improved. And quality-of-life scores improved overall, especially in the areas of physical functioning, social functioning and self-esteem. Some adverse events were observed, including headache and upper respiratory tract infection symptoms, but they were mainly mild.
Since there were marked improvements after the anti–IL-5 therapy, researchers have determined that anti–IL-5 is a promising therapy for eosinophilic esophagitis. Based on these results, the manufacturer of anti-IL-5 is moving ahead with large scale clinical trials.
Fluticasone Propionate as a Potential Therapy
Another trial used fluticasone propionate as a potential treatment for eosinophilic esophagitis. This study is the first randomized, double-blind, placebo-controlled study concerning therapy for eosinophilic esophagitis.
Researchers found that swallowed fluticasone propionate was effective in inducing histologic remission in eosinophilic esophagitis, with a more pronounced effect in non-allergic and younger individuals, and especially in the proximal esophagus. With its ease of administration and favorable side effect profile, researchers concluded that fluticasone propionate is an attractive therapy to treat eosinophilic esophagitis.
Optimal dosing and improved compliance may increase efficacy, and this and other unresolved issues require additional larger clinical trials to refine the therapeutic role of fluticasone propionate in eosinophilic esophagitis. Such trials are now ongoing by the Cincinnati Center for Eosinophilic Disorders.
Eosinophilic Esophagitis
With eosinophilic esophagitis the esophagus is overwhelmed with white blood cells and as a result, patients of all ages develop symptoms that closely resemble illnesses such as acid reflux disease, food allergies and inflammatory bowel disease.
Eosinophilic esophagitis is diagnosed by a combination of testing, including skin allergy tests, but most importantly, it requires analysis of esophageal tissue specimens obtained by endoscopy.
Common treatment includes a combination of medications and a change in diet. Many patients are so allergic to food that they can no longer eat anything. As a result, they are fed a simple elemental diet through a feeding tube. It is a chronic illness, but with proper management, most patients lead functional lives.
Dr. Rothenberg and his team of physicians and researchers, including Philip E. Putnam, MD, and Margaret H. Collins, MD, both of Cincinnati Children's, have shown that eosinophilic esophagitis affects one in 2,000 children in the Cincinnati region. Cincinnati Children's is seeing an increase in cases of eosinophilic esophagitis in many countries, including England, Israel, Japan, Spain, Australia, Switzerland and Italy, and are currently treating 20 international patients.
The Cincinnati Center for Eosinophilic Disorders is a collaboration between the Division of Allergy and Clinical Immunology and the Division of Gastroenterology, Hepatology and Nutrition, as well as researchers.
