OWE-18\u2005Non-responsive and refractory coeliac disease: the largest UK experience from the NHS england national centre

Abstract

Introduction Non-responsive coeliac disease (NRCD) is defined by persisting symptoms or laboratory abnormalities in patients with coeliac disease (CD) despite a gluten-free diet (GFD). Causes of NRCD are heterogeneous, with refractory CD (RCD) being associated with poor prognosis. The aims of this study are to identify the aetiologies for persisting symptoms in patients with NRCD referred to a national UK centre for CD, and to assess mortality rates in each group. Methods Data on all CD patients, including those with persisting symptoms and tertiary referrals, was collected prospectively from 1998–2018. Patients were systematically investigated to establish the aetiology of their continued symptoms. They were also referred to a specialist coeliac dietitian to identify any lapses in GFD adherence or gluten cross-contamination. A repeat duodenal biopsy was performed and compared to previous biopsies where possible to check for histological remission. Colonoscopy, lactose hydrogen breath test, glucose hydrogen breath test, SeHCAT scan, CLO testing, faecal elastase, immunohistochemistry and γ-TCR clonality were performed. Results 2,356 patients with suspected CD were seen in this time period (121 were tertiary referrals). 157 were excluded from analysis due to unconfirmed diagnosis. Of the remaining 2,199 patients with confirmed CD, 2,123 had both villous atrophy and positive IgA-EMA/TTG, and 76 had seronegative CD. Of the 2,199 patients with CD (67% female, mean age at diagnosis 42.8 ± 18.5), 292 (13%) had persisting symptoms. The leading causes for persisting symptoms in patients without RCD (73% female, mean age at diagnosis 35.7 ± 19.2) were: gluten contamination (22%), functional/irritable bowel syndrome (20%), pancreatic exocrine insufficiency (7%), reflux dysmotility (5%), and microscopic colitis (5%). Of a total of 74 patients who were identified with RCD, 56 had RCD I (71% female, mean age at CD diagnosis 41.8 ± 19.0) and 18 had RCD II (33% female, mean age at CD diagnosis 55.4 ± 13.3). After a median follow up of 40.5 months (IQR 21.8–73.3), mortality was 7% in the RCD I group, compared to 39% in the RCD II group (p=0.019). Higher age at diagnosis of CD is a predictor for having RCD in patients with persisting symptoms (p<0.001). Conclusions This is the largest UK study of NRCD and RCD. The contemporary mortality data in RCD II remains poor. Patients with suspected RCD should be referred to the National Centre for consideration of novel therapies such as IL-15 and Stem Cell Transplant.