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Background & Aims: Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury., Methods: This gluten challenge phase 2 trial was double blind and placebo controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine., Results: Fifty patients were randomized, and 43 patients completed the study (IMGX003, n = 21; placebo, n = 22). The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was -0.04 vs -0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P = .231), 0.96 vs 3.29 (bloating, P = .204), and 0.02 vs 3.20 (tiredness, P = .113). The 3 × 2-week trend line significance values for these symptoms, respectively, were P = .014, .030, and .002., Conclusions: IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. (ClinicalTrials.gov, Number: NCT03585478)., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Coeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding., Aim: To determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease., Methods: This was a case-control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age- and gender-matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing., Results: Of 47 557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight-matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2 years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85-1.63, P = 0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P = 0.001)., Conclusion: This study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed., (© 2018 John Wiley & Sons Ltd and Mayo Foundation.)

Background: Therapy for coeliac disease (CD) mainly relies on following a gluten-free diet (GFD); however, a serum marker for gluten intake has yet to be established., Aim: To evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse., Methods: Alkylresorcinol concentrations were compared among treated patients with coeliac disease (n = 34), untreated coeliac disease patients (n = 36) and controls (n = 33). Furthermore, seven additional coeliac disease patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of five mice fed a regular chow and 10 mice fed lifelong with a gluten-free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated., Results: Total alkylresorcinol concentrations were significantly lower in treated with coeliac disease [median (IQR), 3 (2-8) nmol/L], compared to untreated patients [median (IQR), 32 (11-74) nmol/L; P < 0.0001] or healthy controls [median (IQR), 54 (23-112) nmol/L; P < 0.0001]. Moreover, alkylresorcinol concentrations in coeliac disease patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol/L after GFD, P = 0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten-free chow was 1.8 (1.6-2.3) nmol/L, which was further significantly increased to 16 (11-22) nmol/L after 8 days of feeding with the gluten-free chow that had gluten added to it. (P = 0.008)., Conclusion: Serum alkylresorcinol concentrations could be a useful marker for dietary gluten in coeliac disease., (© 2017 John Wiley & Sons Ltd.)

Background: Despite increasing prevalence, the economic implications of coeliac disease are just emerging., Aims: To assess the impact of coeliac disease diagnosis on healthcare costs and the incremental costs associated with coeliac disease., Methods: Administrative data for a population-based cohort of coeliac disease cases and matched controls from Olmsted County, Minnesota were used to compare (i) direct medical costs 1 year pre- and post-coeliac disease diagnosis for 133 index cases and (ii) 4-year cumulative direct medical costs incurred by 153 index cases vs. 153 controls. Analyses exclude diagnostic-related and out-patient pharmaceutical costs., Results: Average total costs were reduced by $1764 in the year following diagnosis (pre-diagnosis cost of $5023 vs. $3259; 95% CI of difference: $688 to $2993). Over a 4-year period, coeliac disease cases experienced higher out-patient costs (mean difference of $1457; P = 0.016) and higher total costs than controls (mean difference of $3964; P = 0.053). Excess average total costs were concentrated among males with coeliac disease ($14,191 vs. $4019 for male controls; 95% CI of difference: $2334 to $20,309)., Conclusions: Coeliac disease-associated costs indicate a significant economic burden of disease, particularly for diseased males. Diagnosis and treatment of coeliac disease reduce medical costs of care suggesting an economic advantage to earlier detection and treatment.

Background and Aims: Celiac disease is considered rare in North America. However, an increasing incidence and widening clinical spectrum have been reported in many countries, and serologic screening suggests a higher prevalence of minimally symptomatic disease. This study reports temporal trends in the incidence of celiac disease in Olmsted County, Minnesota., Methods: All county residents diagnosed with celiac disease between 1950 and 2001 were identified through the Rochester Epidemiology Project. Incidence rates were calculated assuming a Poisson distribution, and changes in incidence by calendar year, age, and gender were assessed by using Poisson regression., Results: Altogether, 82 new cases of celiac disease were identified during the 50-year period. There was a marked female predominance (P < 0.005), and the incidence rates increased with age (P < 0.001) and calendar period (P < 0.001). The overall annual incidence of celiac disease was 2.1 per 100,000 (95% confidence interval [CI], 1.7-2.6) but increased from 0.9 per 100,000 (CI, 0.5-1.2) in 1950-1989 to 3.3 per 100,000 (95% CI, 2.2-4.4) in the 1990s. The incidence was 9.1 per 100,000 (95% CI, 5.2-13.0) in the final 2 years of the study. Serology prompted biopsy in a substantial proportion of recent diagnoses. Clinical features also changed over time, with less diarrhea and weight loss at presentation., Conclusions: Celiac disease has increased recently in this well-characterized population. Milder clinical features and use of serology suggest an increased detection rate, although a true increase in incidence may have also occurred. Celiac disease is not rare in North America.