The Gluten-Free Diet for Celiac Disease and Beyond.

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.

Factores que limitan la adherencia a la dieta y la calidad de vida en enfermos celiacos chilenos durante COVID-19 / Factors that limit adherence to diet and quality of life in Chilean celiac patients during COVID-19

La enfermedad por coronavirus (COVID-19) es altamente contagiosa y las medidas de confinamiento dinámico han demostrado que reducen significativamente el número de contagios, sin embargo, pueden alterar la disponibilidad de alimentos afectando la adherencia a la dieta libre de gluten (DLG) y la calidad de vida (CV) en la enfermedad celiaca (EC). El objetivo de este estudio fue evaluar los factores que limitan, la adherencia a la dieta libre de gluten y la calidad de vida en personas con enfermedad celiaca en periodo de pandemia por COVID-19. Métodos Se aplicaron encuestas on-line respecto a adherencia a la DLG, CV y acerca de los factores que han generado dificultad para llevar una DLG en este escenario. Resultados Se analizaron 216 encuestas de enfermos celiacos, mayores de 15 años, de los cuales un 91% eran mujeres con un promedio de edad de 36 + 10,7 años y con 5,8 + 6,0 años de enfermedad. El 56,48% tenía una excelente adherencia a la DLG y un 43,52% una buena CV. El costo elevado de los alimentos sin gluten fue la pregunta con mayor porcentaje de respuesta, asociándose con regular y mala adherencia a la DLG (valor p=0,001) y con pobre CV (valor p=0,023). Conclusión En periodo de pandemia por COVID-19, el costo de los alimentos se asocia con adherencia regular y mala a la DLG y con pobre CV(AU)

Coronavirus disease (COVID-19) is highly contagious and dynamic confinement measures have shown to significantly reduce the number of infections, however, they can alter the availability of food, affecting adherence to a gluten-free diet (GFD) and quality of life (QoL) in celiac disease (CD). The objective of this study was to evaluate the limiting factors, adherence to a gluten-free diet and quality of life in people with celiac disease in a COVID-19 pandemic period. Methods. On-line surveys were applied regarding adherence to the GFD, CV, and factors that have generated difficulty in carrying out a GFD in this setting. Results. 216 surveys of celiac patients over 15 years of age were analyzed, of which 91% were women with an average age of 36 + 10.7 years and with 5.8 + 6.0 years of the disease. 56.48% had excellent adherence to the GFD and 43.52% had a good QoL. The high cost of gluten-free foods was the question with the highest response percentage, associated with regular and poor adherence to the GFD (p-value = 0.001) and with poor QoL (p-value = 0.023). Conclusion. In a COVID-19 pandemic period, the cost of food is associated with regular and poor adherence to the GFD and with poor QoL(AU)

Healthcare Resource Utilization and Costs in Celiac Disease: A US Claims Analysis.

INTRODUCTION: Celiac disease (CeD) is a lifelong immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction in the small intestine. This retrospective cohort study examines healthcare resource utilization (HRU) and costs between patients with CeD and matched controls. METHODS: Patients with CeD (cases) with an endoscopic biopsy and ≥2 medical encounters with a CeD diagnosis between January 1, 2010, and October 1, 2015, were identified in the MarketScan databases. The date of the first claim with a CeD diagnosis on or after the endoscopic biopsy was the index date. Cases were matched 1:1 to patients without CeD (controls) on demographic characteristics and Deyo-Charlson Comorbidity Index score. Clinical characteristics, all-cause, and CeD-related HRU and costs (adjusted to 2017 US dollars) were compared between cases and controls during the 12 months before (baseline) and 24 months after (follow-up) the index date. RESULTS: A total of 11,008 cases (mean age 40.6 years, 71.3% women) were matched to 11,008 controls. During the follow-up, a higher proportion of cases had all-cause and CeD-related HRU including inpatient admissions, emergency department visits, gastroenterologist visits, dietician visits, endoscopic biopsies, and gastroenterology imaging (all P ≤ 0.002). Incremental all-cause and CeD-related costs were in the first ($7,921 and $2,894) and second ($3,777 and $935) year of follow-up, driven by outpatient services costs. DISCUSSION: In this US national claims database analysis, there was evidence of an increase in both all-cause and CeD-related HRU and related costs in patients with CeD compared with matched patients without CeD, suggesting a significant economic burden associated with CeD.

Costs and Use of Health Care in Patients With Celiac Disease: A Population-Based Longitudinal Study.

INTRODUCTION: Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis. METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n = 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs. RESULTS: Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged <18 years, $715 ($632-803) in ages 18-64 years, and $1,010 ($799-1,230) in ages ≥65 years. Half of all costs were attributed to 5% of the prevalent patients. Annual healthcare costs were $391 higher 5 years before diagnosis and increased until 1 year after diagnosis; costs then declined but remained 75% higher than those of comparators 5 years postdiagnosis (annual difference = $1,044). Although hospitalizations, nonprimary outpatient visits, and medication use were all more common with CD, excess costs were largely unrelated to the prescription of gluten-free staples and follow-up visits for CD. Mucosal healing in CD did not reduce the healthcare costs. DISCUSSION: The use and costs of health care are increased in CD, not only before, but for years after diagnosis. Mucosal healing does not seem to lower the healthcare costs.

Concepts and Instruments for Patient-Reported Outcome Assessment in Celiac Disease: Literature Review and Experts' Perspectives.

BACKGROUND: In diseases where there is a large subjective component, such as celiac disease (CD), patient reported-outcomes (PRO) endpoints are highly relevant. However, there is a gap in knowledge about which PRO endpoints and instruments should be used for clinical trials for treatment of celiac disease. OBJECTIVES: To identify patient-centered symptom, impact, and health-related quality of life (HRQoL) concepts in CD and relevant PRO instruments, and to gather expert input on concepts and instruments to inform selection of PRO endpoints for use in clinical trials of new CD treatments. METHODS: A targeted literature review was conducted to identify symptom, impact, and HRQoL concepts, including those captured in PROs further reviewed against U.S. Food and Drug Administration standards for development and validation as endpoints. US and European clinicians, payers, and a patient advocate (n = 21) were interviewed to assess the identified concepts' relative importance in measuring treatment benefit and to gauge the value of potential PROs as endpoints for market access/reimbursement. RESULTS: Thirty-four published studies were identified: 27 elucidated patient-centered concepts and 7 detailed the development or validation of PRO instruments. The Celiac Disease Symptom Diary and Celiac Disease Patient Reported Outcome instrument were deemed most appropriate for use as endpoints; however, each had limitations related to conceptual coverage, evidence for measurement properties, and feasibility for use in clinical trials. Experts reported gastrointestinal symptoms as most important to treat, with extra-intestinal symptoms burdensome from the patient perspective as well. Payers emphasized measuring both frequency and severity of symptoms and targeting patients nonresponsive to the gluten-free diet for treatment. CONCLUSIONS: With emerging treatment options for CD, further work is needed to operationalize PRO symptom endpoints that are meaningful to patients, valued by payers, and acceptable to regulators in demonstrating efficacy.

Cost of chronic inflammatory disease: The impact of eosinophilic esophagitis in Nevada.

OBJECTIVES: The cost of treating the rare eosinophilic esophagitis (EoE) disease and its impact on patients' quality of life have not been well documented in the literature. This study seeks to fill this gap by comparing the cost of EoE with other well-known inflammatory diseases, including Crohn's disease (CD) and celiac disease (CeD). METHODS: A Mann-Whitney U test and multiple logistic regression were used to examine the cost of EoE in the state of Nevada across all hospital settings and its impact on quality of life compared with CD and CeD. RESULTS: Several factors were associated with the overall cost of EoE in Nevada, including patients' age, sex and region (P < 0.001). EoE was significantly more expensive to treat in the pediatric group ($4001 EoE; $985 CD; $856 CeD), among men ($2532 EoE; $1500 CD; $1724 CeD), among those residing in the southern region of Nevada ($4501 EoE; $2538 CD; $1888 CeD), and among patients seeking medical care from outpatient clinics ($3298 EoE; $741 CD; $1686 CeD) (P < 0.001). Age, sex, region and hospital setting were all associated with having a positive EoE record compared with CeD or CD (P < 0.001). CONCLUSIONS: Data from this study indicate that the EoE burden is significantly higher in cost for certain demographics and regions compared with CD and CeD in the state of Nevada, specifically among pediatric and male patients. These differences suggest that clinicians may encounter similar issues when treating EoE.

Gluten-Free Products: From Dietary Necessity to Premium Price Extraction Tool.

Every year, the Italian National Health Service (NHS) provides about 200,000 celiac people (based on 2017 data) living in Italy with financial support of about 250 million euro to cover the cost of their specific dietary constrains. The existence of gluten-free products of high quality and affordable price is very important for the quality of life of celiac people and the sustainability of public support. Over the last decade, the market for gluten-free products has experienced a dramatic surge, with an increasing shelf space dedicated to these products in supermarkets, and a large variety of products both in terms of kind of agricultural inputs and processing and packaging methods. This study aimed at assessing the offer of gluten-free (GF) pasta in Italian supermarkets, with respect to its ability to meet the needs of celiac people in terms of variety, prices and safety. A hedonic price analysis was performed. Results indicated that GF pasta is sold only in 44% of the 212 stores of the sample, with a price equal to more than twice that of conventional pasta. A premium price was found for the following attributes: small packages, brands specialized in GF products, content in fiber and the presence of quinoa as ingredient.

Persistent Economic Burden of the Gluten Free Diet.

Gluten free (GF) products have been reported to be more expensive and less available than their gluten containing counterparts. We examined the current U.S. cost and availability of GF products and made comparisons to the marketplace over a decade ago. Cost, determined by price per ounce and availability of a "market basket" of regular and GF products across four venues and five geographic regions was compared using a student's t test. GF products were more expensive (overall 183%), and in all regions and venues (p < 0.001). GF products from mass-market producers were 139% more expensive than the wheat-based version of the same product. Availability of GF products was greatest (66%) in the health food and upscale venues. In contrast to the results of the 2006 study, the cost of GF products has declined from 240% to 183% (adjusted for inflation). The introduction of mass-market production of GF products may have influenced the increase in availability and overall reduction of cost since 2006. The extent to which the cost of GF products impacts dietary adherence and quality of life for those on a GFD warrants exploration.

Quality of Life in People with Coeliac Disease: Psychological and Socio- Economic Aspects.

BACKGROUND AND OBJECTIVE: Coeliac disease (CD) is a chronic autoimmune intestinal disorder characterized by intolerance to gluten, a protein contained in certain cereals. The main physiopathological basis of CD is the progressive destruction of intestinal villi caused by gluten ingestion by genetically-susceptible individuals. Patients who receive a diagnosis of CD must make significant changes to their daily habits and this can affect their quality of life. The objective of this review is to summarize the evidence regarding the economic, physical and social limitations which can affect the quality of life in patients with CD. RESULTS: Different factors such as physical changes, psychological effects, interpersonal relationships, emotions and economic difficulties can affect the quality of life of these patients. Observations suggest that, in general, women with CD experience a greater deterioration in their quality of life than men. Lastly, complications in daily life are also associated with the reduced availability of gluten-free products which also usually cost more than standard products. CONCLUSIONS: Continuous health education and care regarding socio-economic issues should be continuously developed and provided to people with CD.

Systematic Literature Review of the Economic Burden of Celiac Disease.

BACKGROUND: The prevalence of celiac disease (CD) has rapidly increased over recent decades, but costs related to CD remain poorly quantified. OBJECTIVE: This systematic review assessed the economic burden of CD in North America and Europe. METHODS: MEDLINE, EMBASE, EconLit, and the Cochrane Library databases were systematically searched to identify English-language literature from 2007 to 2018 that assessed costs, cost effectiveness, and health resource utilization for CD. RESULTS: Forty-nine studies met the inclusion criteria, of which 28 (57.1%) addressed costs of testing and diagnosis; 33 (67.3%) were from Europe. The cost per positive CD diagnosis of testing patients already undergoing esophagogastroduodenoscopy for other indications ranged from 1300 Canadian dollars ($Can) in Canada (2016 value) to €44,712 in the Netherlands (2013 value). Adding the CD test was cost effective when it combined diagnostic modalities (e.g., serology and biopsy). Direct annual excess costs to a US payer per diagnosed CD patient totaled $US6000 (2013 value) more than for a person without CD, chiefly due to outpatient care. Hospitalizations, emergency visits, and medication use were more common with CD. After initiating a gluten-free diet (GFD), patients visited primary care providers less often, used more medications, and missed fewer days from school and work. CONCLUSIONS: Most of the few available economic studies of CD assess testing and diagnosis costs, especially in Europe. Methods of testing generally are considered cost effective when they combine diagnostic modalities in symptomatic patients. Most costs to a payer of managing CD derive from outpatient care. Following GFD initiation, patients lose fewer days from work and school than pretreatment.

The Nutritional Quality of Gluten-Free Products for Children.

OBJECTIVES: To examine the nutritional quality of gluten-free (GF) products specifically marketed for children. METHODS: All child-targeted food products were purchased from 2 major supermarket chains in Calgary, Alberta, Canada. Using the Pan American Health Organization Nutrient Profile Model, the nutritional quality of products with a GF claim was compared with those without such a claim. A secondary analysis further compared the nutrient profile of child-targeted GF products to their product "equivalents." RESULTS: Overall, child-targeted GF products had lower levels of sodium, total fat, and saturated fat but also had less protein and a similar percentage of calories from sugar compared with child-targeted products without a GF claim. According to the Pan American Health Organization criteria, both GF products and "regular" products designed for children can be classified as having poor nutritional quality (88% vs 97%; P < .001). When analyzed in light of their product equivalents without a GF claim, both had similarly high levels of sugar (79% vs 81%; P < .001). CONCLUSIONS: GF supermarket foods that are targeted at children are not nutritionally superior to regular child-targeted foods and may be of greater potential concern because of their sugar content. The health halo often attributed to the GF label is not warranted, and parents who substitute GF products for their product equivalents (assuming GF products to be healthier) are mistaken. Parents of children with gluten intolerance and/or sensitivity, along with parents who purchase GF products for other health reasons, need to carefully assess product labels when making purchases.

Screening for coeliac disease in children.

AIM: Coeliac disease is a common but markedly under-diagnosed condition, which may lead to serious long-term complications if untreated. Both the diagnostic yield and true incidence have significantly increased during the last few decades and it is now one of the most common chronic gastrointestinal conditions in children. The aim of this review was to summarise the current concepts on screening for coeliac disease in children and adolescents. METHOD: We conducted a non-systematic literature review of papers published about coeliac disease screening since the year 2000. RESULTS: Our review showed that the diagnostic yield could be significantly improved by screening for at-risk groups, or even the whole population, but these approaches remain controversial. Evidence suggests that screening for certain high-risk groups could be beneficial, but untargeted mass screening is not currently recommended. However, whether the benefits of an early diagnosis would overcome the challenges of lifelong dietary treatment, especially in asymptomatic individuals who consider themselves healthy, are unclear. CONCLUSION: There is moderate evidence that screening certain at-risk groups for coeliac disease could be beneficial, but more studies in different settings are needed before large-scale population screening can be recommended.

E-Healthcare for Celiac Disease-A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate the (cost-)effectiveness of online consultations in follow-up of patients with celiac disease (CD). STUDY DESIGN: Multicenter randomized, controlled trial involving 304 patients aged ≤25 years with CD for ≥1 year, randomized to an online (n = 156) or outpatient consultation (n = 148). An online consultation included questionnaires for symptom and growth measurement. Antitransglutaminase-type-2 antibodies were determined using a point-of-care (POC) test. Controls had a traditional consultation with antitransglutaminase-type-2 antibodies testing in laboratories. Both groups completed questionnaires concerning CD-specific health-related quality of life (HRQOL), gluten-free diet adherence, and patient satisfaction. Six months later, participants repeated HRQOL and patient satisfaction questionnaires and the POC test. The primary outcome was anti-transglutaminase-type-2 antibodies after 6 months, and the secondary outcomes were health problems, dietary adherence, HRQOL, patient satisfaction, and costs. RESULTS: The performance of the POC test was inferior to laboratory testing (2/156 positive POC tests vs 13/148 positive laboratory tests; P = .003). Health problems were detected significantly more frequently using online consultation. The detection of growth problems and dietary transgressions was similar. HRQOL (from 1 [good] to 5 [poor]) improved after online consultation (from 3.25 to 3.16 [P = .013] vs controls from 3.10 to 3.23; P = .810). Patient satisfaction (from 1 [low] to 10 [high]) was 7.6 (online) vs 8.0 (controls; P = .001); 58% wished to continue online consultations. Mean costs per participant during the studied period were €202 less for the online group (P < .001). CONCLUSIONS: The primary outcome could not be tested because the POC test was unreliable. Nevertheless, our results indicate that online consultations for children and young adults with CD are cost saving, increase CD-specific HRQOL, and are satisfactory for the majority. TRIAL REGISTRATION: Trialregister.nl: NTR3688.

Implementation of National Institute for Health and Care Excellence (NICE) guidance to measure immunoglobulin A with all coeliac screens: can an affordable solution be devised?

There has been a dramatic increase in requests for coeliac disease (CD) serological screening using immunoglobulin (Ig)A tissue transglutaminase antibodies (IgA-tTG). Recently, the UK National Institute for Health and Care Excellence has revised its guidance, recommending that total IgA should also be measured in all samples. This is justified, as false-negative results may occur with IgA deficiency. However, implementation of this guidance will incur considerable expense. Tests that measure IgA-tTG antibodies can detect IgA deficiency, indicated by low background signal. This provides an opportunity to identify samples containing IgA ≤ 0·2g/l, obviating the need for unselected IgA measurement. We investigated the feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® enzyme-linked immunosorbent assay to quantify IgA-tTG antibodies. In both cases, total IgA correlated strongly with background IgA-tTG assay signal. Using the Celikey™ assay, a threshold of < 17·5 response units achieved 100% sensitivity (95% confidence intervals 79·4-100%) for detection of IgA ≤ 0·2g/l, circumventing the need for IgA testing in > 99% of sera. A similar principle was demonstrated for the QUANTA Lite® assay, whereby a threshold optical density of < 0·0265 also achieved 100% sensitivity (95% confidence intervals 78·2-100%) for IgA ≤ 0·2 g/l, avoiding unnecessary IgA testing in 67% of cases. These data suggest that CD screening tests can identify samples reliably containing low IgA in a real-life setting, obviating the need for blanket testing. However, this approach requires careful individualized validation, given the divergent efficiency with which assays identify samples containing low IgA.

The unknown burden and cost of celiac disease in the U.S.

INTRODUCTION: Celiac disease is an autoimmune disease that results from exposure to gluten in genetically susceptible individuals and leads to a range of gastrointestinal and extraintestinal symptoms. Areas covered: In order to evaluate the literature with respect to burden associated with celiac disease in the U.S. and identify any knowledge gaps, we performed a literature review of journal articles published between 2000-2016. We note that celiac disease is a prevalent condition associated with a significant burden of disease through its impact on morbidity, quality of life, as well as through increased costs associated with its diagnosis and management. At the same time, knowledge gaps exist in our understanding of the precise epidemiologic burden in the U.S.; the trade-offs between burden and benefit of a gluten-free diet; and better estimation of the costs of diagnosis, treatment and management.Expert commentary: Additional research is necessary to better understand these gaps to be able to reduce burden of celiac disease, particularly the impact on health-related quality of life and the costs associated with inaccurate or delayed diagnoses and insufficient treatment of disease.

Coping with celiac disease: how heavy is the burden for caregivers?

Background: Celiac disease (CD) is the most common chronic enteropathy demanding a lifelong gluten-free diet. Objective: The aim of the study was to identify and estimate the subjective burden of caregivers of celiac patients. Methods: A cross-sectional observational study was conducted during the regional meeting of the Italian Society for the Celiac Disease in April 2014. A written self-administered anonymous questionnaire enquired into caregivers’ demographic profile, natural history of patients’ disease and caregivers’ self-reported degree of burden at the onset of symptoms (T0), at CD diagnosis (T1) and during follow-up (T2). Fifty-five caregivers completed the questionnaire (69% females, 47 ± 13 years old, 73% first-degree relatives). Results: The presence of warning symptoms, such as abdominal pain, chronic diarrhea and weight loss was responsible for higher levels of concern. A statistically significant reduction of concern in the follow-up was demonstrated by the comparison of visual analogue scales (VAS) values from T0 to T2 and from T1 to T2 (6.8 ± 3.1 vs 4.2 ± 2.9 and 7.0 ± 2.5 vs 4.2 ± 2.9, respectively; p < 0.001), mirroring the reduction of distress among newly diagnosed individuals. A global impact of gluten-free diet and CD on quality of life was reported in VASs (6.7 ± 2.4). Family (5.4 ± 3.1), social (5.6 ± 2.9) and economic (4.5 ± 3.4) domains were the most associated. Conclusion: The assessment of caregivers’ subjective burden should be considered as an essential step in the evaluation of celiac patients, needing a specific investigation and support (AU)

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HLA genotyping as first-line screening tool for coeliac disease in children with juvenile idiopathic arthritis.

OBJECTIVES: Coeliac disease (CD) and juvenile idiopathic arthritis (JIA) often coexist. This association warrants assessment for CD in patients with JIA. We evaluated the clinical relevance and cost-effectiveness of human leucocyte antigen (HLA) genotyping in first-line screening for development of CD in children with JIA. PATIENTS AND INTERVENTIONS: 95 patients with JIA were screened for CD using CD-specific antibodies. In case of positivity, a small intestinal biopsy was performed to confirm diagnosis. In addition, HLA genotyping was performed. 110 age-matched and sex-matched Caucasian children from the same geographical area served as controls. RESULTS: CD was diagnosed in 4 of 95 patients with JIA (4.2%), a rate significantly higher compared with controls (p<0.02) and 14 times higher than in the general population. Twenty-six patients (27.4%) had one of the variants of the risk genotypes. All four patients diagnosed with CD had a HLA-DQ2.5 genotype: one was homozygote, the remainder heterozygote. Twenty-two patients are, judging by their HLA genotypes, at risk of developing CD and require repeated serological screening. None of the 69 patients without HLA-DQ2/DQ8 genotypes had CD-specific antibodies. Screening with HLA genotyping becomes cheaper than screening without after the second determination. CONCLUSIONS: In our cohort of patients with JIA, lack of HLA-DQ2/DQ8 genotypes identified a majority not at risk of CD in whom repeated serological testing is unnecessary. Genotyping is nowadays the most efficient and cost-effective way to screen for CD risk in JIA.