The findings, reported in the New England Journal of Medicine, hold out the hope of a treatment for the condition. Currently, the only strategy known to work is embracing a strict gluten-free diet.
"We were finally happy that this works so well," chief author Dr. Detlef Schuppan, director of the Institute of Translational Immunology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany, told Reuters Health in an email.
"Patients and specialists as well are quite excited, since this is the first drug that really works" based on hard endpoints, he said.
His team enrolled 163 adults with well-controlled celiac disease who underwent a daily gluten challenge.
Treatment with the drug, known as ZED1227, at all three dosages attenuated gluten-induced duodenal mucosal injury compared to placebo. The estimated difference from placebo in the change in the mean ratio of villus height to crypt depth at six weeks was 0.44 in the 10-mg group (P=0.001), 0.49 in the 50-mg group (P<0.001), and 0.48 (95% CI, 0.20 to 0.77) in the 100-mg group (P<0.001).
"Use of the 100-mg dose may have improved symptom and quality-of-life scores," the authors said.
The drug, developed by Dr. Falk Pharma, also produced reductions in intraepithelial lymphocyte density, a measure of inflammation due to gluten exposure.
The benefits in the 159 volunteers were assessed using a daily gluten challenge of 3 grams contained in a biscuit.
Celiac disease is an autoimmune disease that affects up to 2% of the population and is triggered by ingesting gluten from wheat, barley or rye. The condition can spark a wide variety of symptoms from fatigue to diarrhea and anemia.
Even with a strict gluten-free diet, only 50% of patients recover.
At the beginning of the study, the ratio of villus height to crypt depth was 1.98 in the placebo group and ranged from 2.01 to 2.09 in the three treatment groups.
After 6 weeks of challenges, the ratio had dropped to 1.39 among those getting placebo and ranged from 1.85 in the low-dose group to 1.94 in the high-dose group (P=0.001 and lower).
The change in the intraepithelial lymphocyte density declined by 2.7 cells per 100 with the 10-mg dose, 4.2 cells in the 50-mg dose, and 9.6 with 100 mg.
"With the exception of rash, which occurred in 3 patients (8%) in the 100-mg group, no adverse events appeared to be more common in the ZED1227 groups than in the placebo group," the researchers said.
There was not a clear dose-response effect.
On the 65-point Celiac Symptom Index, the challenge produced a 4-point increase in symptoms in the placebo group and increases ranging from 0.1 to 2.0 in the three treatment groups. The highest dose was most effective at quelling symptoms and the middle dose was the least effective.
On the Celiac Disease Questionnaire, which has scores ranging from 28 to 196 (higher number signifies a better quality of life), placebo recipients saw a 2.1-point decline from baseline. The highest and lowest doses of ZED1227 produced increases of 3.7 and 3.2 points, respectively, but the middle dose produced an increase of 0.9. None of the changes from baseline were statistically significant.
Dr. Schuppan said the lack of a dose response was not troubling. "Complaints in celiac patients are often unrelated to active celiac disease, e.g., irritable bowel syndrome; however, quality of life was improved at all doses as well as the celiac symptom index subscore," he noted.
"Improved patient-reported outcomes across the dose groups need to be confirmed in a larger study, since they may reflect the rather small size of each group for the evaluation of symptoms or the scales capturing some symptoms that may overlap with, but are unrelated to, celiac disease," the researchers said.
Dr. Schuppan said a phase 2b-3 trial of 400 patients at 30 European centers is set to begin this fall.
SOURCE: https://bit.ly/2Une2Bv The New England Journal of Medicine, online July 1, 2021.
By Gene Emery
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