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CHICAGO (FRONTLINE MEDICAL NEWS) – A thrice-daily regimen of open-capsule budesonide has the potential to manage a rare and severe illness – adult autoimmune enteropathy (AIE) – according to Ayush Sharma, MD.
Most patients who received the treatment responded to it, with about half experiencing a complete cessation of the chronic diarrhea that is the clinical hallmark of adult autoimmune enteropathy, Dr. Sharma said at the annual Digestive Disease Week®.
Joseph Murray, MD , of the Mayo Clinic, Rochester, Minn., pioneered the open-capsule technique as a way of delivering topical steroid therapy to patients with treatment-refractory celiac disease. This latest study, presented by his Mayo colleague, Dr. Sharma, confirms that open-capsule budesonide is equally effective treatment for AIE.
“AIE is a very rare disease, with only about 50 cases reported in the literature,” said Dr. Sharma. But part of its rarity may result from misdiagnosis. AIE is frequently mistaken for severe treatment-refractory celiac disease. Both are clinically characterized by refractory diarrhea, malabsorption of nutrients, and anorexia. However, unlike celiac disease, which is caused by genetic gluten intolerance and limited to the large intestine, AIE is a pangastrointestinal disorder that also involves the pancreas and liver. On histology, the small intestine displays often complete villous atrophy. AIE also has a very specific immune marker: gut epithelial cell antibodies, which attack enterocytes and goblet cells. These cells are often completely absent as the disease progresses.
AIE has typically been treated with immunosuppressive therapy, including corticosteroids and azathioprine. Resistant cases have been treated with adalimumab, infliximab, and tacrolimus, which are moderately successful. Because it’s an autoimmune disorder, patients need long-term maintenance therapy, which exposes them to all the risks associated with these powerful medicines.
Recently, physicians at the Mayo Clinic have adopted Dr. Murray’s open-capsule budesonide regimen as an AIE treatment. It employs three daily doses of 3-mg enteric-coated budesonide capsules, which are consumed in three different ways:
Dr. Sharma presented a retrospective analysis comparing patient characteristics and treatment response among 43 patients with treatment-refractory celiac disease (RCD) and 26 with AIE. Patients were treated at the Mayo Clinic in Rochester from 2001 to 2016.
AIE patients were younger than RCD patients (44 vs. 57 years) and, more often, male (62% vs. 28%). They were more likely to report diarrhea (100% vs. 70%), weight loss (84% vs. 69%), and fatigue (50% vs. 14%), and to be on total parenteral nutrition (35% vs. 7%).
A large proportion (69%) had tried a gluten-free diet, but none responded to it. Gut epithelial cell antibodies were often present (82% of AIE patients vs. 12.5% of RCD patients). AIE patients more often had hypoalbuminemia (64% vs. 16%). Nearly half (46%) showed complete villous atrophy, compared with 30% of those with RCD. However, they showed intraepithelial lymphocytes less often than did those with RCD (54% vs. 91%).
Patients in both the AIE and RCD cohorts were initially treated with other drugs, including azathioprine (27% and 35%, respectively) and systemic corticosteroids (96% and 14%). Only three of the AIE patients responded well to these. Additionally, about a quarter of each cohort had already taken a course of enteric-coated budesonide, but none had responded to it. All patients except the three responders were given a trial of open-capsule budesonide.
Clinical response was defined as complete cessation of diarrhea after treatment. Partial response was an improvement in stool frequency or weight gain but not complete resolution. After subtracting the numbers lost to follow-up and the patients who responded to initial therapy, clinical outcomes were available for 17 AIE patients and 37 RCD patients (about 85% of each group).
Almost half of those with AIE (8; 47%) and a majority of those with RCD (25; 68%) experienced a complete response to open-capsule budesonide. A partial response occurred in seven of those with AIE (41%) and nine of those with RCD (24%). Only two patients with AIE and three with RCD failed to respond to the regimen.
“We were very happy to see that 89% of our AIE patients responded to open-label budesonide,” Dr. Sharma said. “We need prospective clinical trials of this treatment. Open-label budesonide may be useful as an initial treatment in AIE, with the benefit of a safer therapeutic profile than systemic steroids.”
Dr. Sharma had no relevant financial disclosures.
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