MAY 30, 2018

Antibody Offers New Hope For Celiac Disease Patients

WRITTEN BY: Nouran Amin

Celiac disease is genetically predisposed to hereditary disease and a serious autoimmune disorder that can damage the small intestine upon the ingestion of gluten. Roughly 1 in 100 people are affected worldwide and about two and one-half million Americans are undiagnosed or are at risk for long-term health complications.

When individuals with celiac disease ingest gluten (a protein found in wheat, rye, and barley), their body produces an immune response that attacks the small intestine; leading to damage of the villi where nutrients cannot be absorbed properly. As of now, the only treatment for celiac disease is avoiding any gluten-contained foods; strictly gluten-free diet. Individuals with celiac disease must avoid foods with wheat, rye, and barley, such as bread and beer. Sometimes, these individuals might accidentally ingest small amounts of gluten which unfortunately can trigger small intestine damage.

Now, investigators have found an antibody by the name of AMG 714 may reduce symptoms of gluten exposure. AMG 174 works to inhibit interleukin-15, a crucial mediator of celiac disease. "It's important to note that this drug is being investigated for its potential to protect against modest contamination, not deliberately eating large amounts of gluten, like bread or pasta," said Francisco Leon, MD, PhD, the study director and consultant for Amgen. "Contamination, which can happen during food processing or packaging, during cooking, or due to inadequate labeling, is known to occur very frequently, despite following a gluten-free diet. Our hope is that this drug may allow celiac patients on a gluten-free diet to experience fewer gluten-triggered events."

Results of the research study showed that the antibody, AMG 714, decreased gluten-triggered effects of celiac patients that were administered the drug in comparison to a placebo. Although AMG 714 did not completely prevent gluten-induced mucosal injury in patients of the “gluten challenge group”, the main endpoint of this study, a reduction in intestinal inflammation was examined, as well as a non-significant trend towards decreased intestinal damage in patients of the “non-challenge group”. A decrease in symptoms was observed when patient-reported outcomes were examined, especially for patients that took a larger drug dose of 300. While the placebo group had an increase in diarrhea, these symptoms were not apparent in patients who took the drug. By week 12, not a single patient administered the 300 mg dose was declared by the principal investigator to have active disease, compared to only one-third of the patients in the placebo group. For the group that did not receive the gluten challenge, there were no symptoms that were evident to be associated with accidental gluten consumption. Most importantly, no serious adverse events or noted dangers were seen in the study. Most complications that were reported included the study drug injection site reactions and pain. Headaches and upper respiratory tract infections were also reported. Additionally, dose-related trends were not evident with the exception of injection site reactions. "A gluten-free diet has been the only treatment option for celiac disease patients to date, yet it is nearly impossible for them to avoid gluten entirely and indefinitely," said Markku Maki, MD, PhD, the principal investigator and a professor for the Faculty of Medicine and Biosciences at the University of Tampere in Finland. "An average of half of all celiac disease patients on a gluten-free diet continue to have mucosal inflammation or damage, and a third have recurrent symptoms. That is why we have been investigating medications to help prevent the consequences of hidden gluten.

 

Source: Digestive Disease Week