Coeliac Disease (CD) Quiz
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Questions and Answers

What is the estimated percentage of non-adherence to a gluten-free diet (GFD) among individuals with coeliac disease?

  • 20%
  • 40%
  • 30%
  • 50% (correct)

    • What is the primary goal of researchers exploring new drug-based therapeutic strategies for coeliac disease?

  • To replace the gluten-free diet with a pharmaceutical treatment
  • To develop a cure for coeliac disease
  • To provide adjunctive therapy and enable gluten re-introduction (correct)
  • To enhance the effectiveness of the gluten-free diet

    • What is the underlying cause of coeliac disease according to the given text?

  • Genetic susceptibility to gluten (correct)
  • Inflammation of the small bowel mucosa
  • Malabsorption of nutrients
  • Immunological response to gluten

    • What has been observed in the clinical presentation of coeliac disease over the past few decades?

    <p>A trend towards an increased symptomatic prevalence</p> Signup and view all the answers

    What is the primary effect of gluten on individuals with coeliac disease?

    <p>Damage to the small bowel mucosa</p> Signup and view all the answers

    What is the current treatment for coeliac disease?

    <p>A strict gluten-free diet</p> Signup and view all the answers

    What is the primary benefit of regular contact with a dietitian for coeliac disease patients?

    <p>To improve quality of life</p> Signup and view all the answers

    What is the maximum amount of gluten that can cause an immune response?

    <p>20 mg per day</p> Signup and view all the answers

    What is the mainstay of treatment for coeliac disease?

    <p>Lifelong gluten-free diet</p> Signup and view all the answers

    Why is it important to know how patients react to a gluten challenge?

    <p>To test new treatments</p> Signup and view all the answers

    What is the purpose of educating patients on how to read ingredient lists and allergen warnings?

    <p>To prevent prolonged exposure to gluten</p> Signup and view all the answers

    What is the potential benefit of targeting the unfolded protein response (UPR) in CD patients?

    <p>Reducing inflammation responses</p> Signup and view all the answers

    What is the primary goal of Treg1-based immunotherapy in CD patients?

    <p>Inducing tolerance against gluten</p> Signup and view all the answers

    What is the potential benefit of JAK/STAT inhibitors in CD patients?

    <p>Reducing inflammation responses</p> Signup and view all the answers

    What is the primary challenge in developing pharmacotherapy for CD?

    <p>Inhibiting the adaptive immune response</p> Signup and view all the answers

    What is the potential benefit of a gluten-free diet in adult CD patients?

    <p>Reducing risk of lymphoma and fractures</p> Signup and view all the answers

    What is the primary trigger for the multifactorial illness of Coeliac disease?

    <p>Gluten ingestion</p> Signup and view all the answers

    What percentage of Coeliac patients possess DQ2?

    <p>95-97%</p> Signup and view all the answers

    What is the gold standard for Coeliac disease diagnosis?

    <p>Endoscopy and small-bowel biopsy</p> Signup and view all the answers

    What is the effect of strict adherence to a gluten-free diet on gut lesions?

    <p>Recovery of gut lesions</p> Signup and view all the answers

    What is the association between female sex and Coeliac disease?

    <p>Female sex is associated with obesity and Coeliac disease</p> Signup and view all the answers

    What is the prevalence of Coeliac disease in the general population in Spain, France, Italy, and Finland?

    <p>0.1-1%</p> Signup and view all the answers

    What is the impact of undiagnosed or untreated Coeliac disease on quality of life?

    <p>Altered quality of life</p> Signup and view all the answers

    What is the purpose of a referral to a dietitian with a special interest in Coeliac disease?

    <p>To develop a gluten-free diet</p> Signup and view all the answers

    What is the result of long-term adherence to a gluten-free diet?

    <p>Recovery of gut lesions</p> Signup and view all the answers

    What is the association between Coeliac disease and candida/saccharomyces?

    <p>Coeliac disease is associated with a higher risk of candida/saccharomyces</p> Signup and view all the answers

    What is the primary reason why pharmaceutical interventions to treat coeliac disease (CD) have been viewed as a compelling and realistic approach?

    <p>The expectation is that therapeutically effective doses of exogenous enzymes will be high</p> Signup and view all the answers

    What is the main characteristic of the 33-mer gluten peptide that persists in the small intestine?

    <p>It is highly resistant to degradation by gastric, pancreatic, and intestinal brush border peptidases</p> Signup and view all the answers

    What is the primary mechanism of action of traditional prescription oral PEP therapeutics?

    <p>Direct activity towards IPP cleavage, decreasing DQ2 and DQ8-mediated T cell recognition</p> Signup and view all the answers

    What is the primary indication for the use of immunosuppressive agents such as azathioprine or methotrexate in patients with coeliac disease?

    <p>RCD or type II refractory CD with high risk of clonality proliferation</p> Signup and view all the answers

    What is the primary limitation of a gluten-free diet (GFD) in treating coeliac disease?

    <p>All of the above</p> Signup and view all the answers

    What is the primary goal of using pharmacologically-based immunomodulatory agents in treating coeliac disease?

    <p>Suppressing the immune response to gluten</p> Signup and view all the answers

    What is the current status of pharmacological interventions for coeliac disease?

    <p>Pharmacological interventions are still in the experimental stages</p> Signup and view all the answers

    What is the primary benefit of using prolyl endopeptidases (PEPs) in treating coeliac disease?

    <p>They can degrade the 33-mer gluten peptide faster than stomach proteases</p> Signup and view all the answers

    What is the primary challenge in developing pharmacological interventions for coeliac disease?

    <p>Developing a pharmacological intervention that can effectively break down gluten</p> Signup and view all the answers

    What is the primary advantage of using AN-PEP as a dietary supplement?

    <p>It can degrade the 33-mer gluten peptide faster than stomach proteases</p> Signup and view all the answers

    What is the primary challenge in developing a treatment for coeliac disease?

    <p>All of the above</p> Signup and view all the answers

    Which molecule is a key regulator of inflammatory processes in coeliac disease?

    <p>NF-kB</p> Signup and view all the answers

    What is the current treatment for coeliac disease?

    <p>A life-long strict gluten-free diet</p> Signup and view all the answers

    What is the result of the abnormal immune response against ingested dietary gluten in coeliac disease?

    <p>All of the above</p> Signup and view all the answers

    What is the association between coeliac disease and Hashimoto thyroiditis?

    <p>The possibility of the common use of two drugs: levothyroxine and methimazole</p> Signup and view all the answers

    What is the concern with PPIs in untreated CD?

    <p>The inhibitory effect on common PEPs</p> Signup and view all the answers

    What is the potential use of several drugs in the treatment of CD?

    <p>Drugs that are mainly used for other diseases</p> Signup and view all the answers

    What is the result of the strict gluten-free diet on patients' behavior?

    <p>Increased exposure to various environmental hazards</p> Signup and view all the answers

    What is the effect of coeliac disease on the risk of early death?

    <p>A 21% increase in the adjusted hazard ratio for early death</p> Signup and view all the answers

    What is the potential target for CD therapy?

    <p>All of the above</p> Signup and view all the answers

    What is the primary target of novel non-dietary therapies for celiac disease?

    <p>All of the above</p> Signup and view all the answers

    What is the current limitation of the gluten-free diet for celiac disease?

    <p>It is suboptimal and lacks complete mucosal healing</p> Signup and view all the answers

    What is the purpose of the Tampere Recommendations for celiac disease trials?

    <p>To establish outcome measures</p> Signup and view all the answers

    What is the mechanism of action of larazotide acetate in celiac disease?

    <p>It is a zonulin-1 antagonist</p> Signup and view all the answers

    What is the role of anti-IL-15 antibodies in celiac disease?

    <p>They interrupt cytokine release and cytotoxic effects</p> Signup and view all the answers

    What is the benefit of targeting the immune system in celiac disease?

    <p>It may induce immune tolerance</p> Signup and view all the answers

    What is the current challenge in developing pharmacotherapy for celiac disease?

    <p>Developing safe and effective treatments</p> Signup and view all the answers

    What is the potential benefit of vilazodone in celiac disease?

    <p>It may alleviate diarrhea-predominant IBS</p> Signup and view all the answers

    What is the goal of novel therapies for celiac disease?

    <p>To induce immune tolerance</p> Signup and view all the answers

    What is the current trend in celiac disease research?

    <p>Exploration of novel non-dietary therapies</p> Signup and view all the answers

    What is the primary objective of the adjunctive use of specific drugs acting against gluten?

    <p>To improve gluten hydrolysis in the gastrointestinal tract</p> Signup and view all the answers

    What is the function of ZED1227?

    <p>To inhibit the amplification step of the gluten immune response</p> Signup and view all the answers

    What is the goal of immune modulation therapies in CD?

    <p>To dampen the local intestinal immune response</p> Signup and view all the answers

    What is the effect of pridopidine on gluten peptides?

    <p>It inhibits the immunogenic potentials of gluten peptides</p> Signup and view all the answers

    What is the current limitation of a gluten-free diet in CD?

    <p>It is difficult to maintain due to its negative social and economic impact</p> Signup and view all the answers

    What is the goal of therapeutic agents targeting key pathophysiological pathways of CD?

    <p>To modulate the immune response to gluten</p> Signup and view all the answers

    What is the function of amylase/trypsin inhibitor in CD?

    <p>To reduce macrogliadin-induced T-cell proliferation</p> Signup and view all the answers

    What is the benefit of IL-2/JES6-1 complex in CD?

    <p>It induces the expansion of Tregs in CeD subjects</p> Signup and view all the answers

    What is the goal of enzyme therapy in CD?

    <p>To break down gluten peptides into smaller fragments</p> Signup and view all the answers

    What is the potential benefit of a rotation diet in CD?

    <p>It reduces the immune response to gluten</p> Signup and view all the answers

    What is the primary mechanism of action of ALV003 in the treatment of coeliac disease?

    <p>It directly degrades gluten, preventing gluten internalization.</p> Signup and view all the answers

    What is the purpose of adding a mucolytic enzyme to ALV003, resulting in DS2016?

    <p>To improve the degradation of gluten, enhancing the efficacy of ALV003.</p> Signup and view all the answers

    What is the primary outcome of the open-label single-arm randomized withdrawal phase 2b study of larazotide acetate?

    <p>A similar benefit compared to GFD, with no significant difference.</p> Signup and view all the answers

    What is the primary advantage of Atvaercept, a mixed IL-2/IL-15 antagonist, in the treatment of coeliac disease?

    <p>It improves histological and serological duodenal lesions.</p> Signup and view all the answers

    What is the primary target of glutenase enzymes in the treatment of coeliac disease?

    <p>The toxic peptides released from gluten, degrading them into smaller, non-immunogenic peptides.</p> Signup and view all the answers

    What is the primary benefit of combining glutenase enzymes with pepsin in the treatment of coeliac disease?

    <p>It improves the degradation of gluten, enhancing the efficacy of glutenase enzymes.</p> Signup and view all the answers

    What is the primary outcome of clinical trials evaluating the efficacy of glutenase enzymes in coeliac disease?

    <p>A reduction in GI symptoms after gluten intake when administered together with a meal.</p> Signup and view all the answers

    What is the primary challenge associated with the gluten-free diet (GFD) in the treatment of coeliac disease?

    <p>The high dedication required to maintain GFD, making it difficult for patients to adhere to.</p> Signup and view all the answers

    What is the primary benefit of novel therapeutic approaches, such as ALV003 and larazotide acetate, in the treatment of coeliac disease?

    <p>They enhance the efficacy of GFD, reducing symptoms and improving quality of life.</p> Signup and view all the answers

    What is the primary goal of pharmaceutical companies in developing novel therapeutic approaches for coeliac disease?

    <p>To improve the efficacy of GFD, reducing symptoms and improving quality of life.</p> Signup and view all the answers

    What is the primary goal of preventing the immune mediated intestinal injury in celiac disease?

    <p>To prevent the activation of the innate immunity</p> Signup and view all the answers

    What is the role of dietitians in the management of celiac disease?

    <p>To educate patients on reading food packaging and identifying gluten-containing components</p> Signup and view all the answers

    What is the primary benefit of enhancing the regeneration of the intestinal mucosa in celiac disease?

    <p>To promote the differentiation of intestinal stem cells into epithelial cells</p> Signup and view all the answers

    What is the primary reason why pharmacological strategies are being explored for the treatment of celiac disease?

    <p>Because the gluten-free diet is not a cure for celiac disease</p> Signup and view all the answers

    What is the primary challenge in developing pharmacological interventions for celiac disease?

    <p>Lack of standardized basis for prescription and use in clinical practice</p> Signup and view all the answers

    What is the role of glucocorticoids in the treatment of celiac disease?

    <p>To reduce the risk of autoimmune refractory celiac disease</p> Signup and view all the answers

    What is the primary goal of patient education and counseling in celiac disease?

    <p>To ensure compliance to medications and prevent drug-nutrient interactions</p> Signup and view all the answers

    What is the primary benefit of using a gluten-free diet in celiac disease?

    <p>To reduce the risk of gluten toxicity</p> Signup and view all the answers

    What is the primary limitation of a gluten-free diet in celiac disease?

    <p>It is not a cure for celiac disease</p> Signup and view all the answers

    What is the primary goal of research in pharmacological interventions for celiac disease?

    <p>To develop a cure for celiac disease</p> Signup and view all the answers

    What is the primary benefit of using small inhibitory RNA in CD therapy?

    <p>Selectively silencing genes that encode HLA-DQ2 and HLA-DQ8</p> Signup and view all the answers

    What is the mechanism of action of natalizumab in treating refractory CD?

    <p>Blocking the integrin alpha4beta7 on the surface of T cells</p> Signup and view all the answers

    What is the potential benefit of using vedolizumab in CD therapy?

    <p>Blocking the traffic of mucosal T cells to the gut</p> Signup and view all the answers

    What is the primary target of cilengitide in CD therapy?

    <p>Integrin alphaVbeta3</p> Signup and view all the answers

    What is the potential benefit of using rebrocabilimab in CD therapy?

    <p>Inhibiting the chemokine receptor CCR9</p> Signup and view all the answers

    What is the primary goal of using anti-CD3 visilizumab in CD therapy?

    <p>Selectively eliminating colorectal T lymphocytes</p> Signup and view all the answers

    What is the primary benefit of the micronutrient-conjugated, ZOT-R-inactivating monoclonal antibody in the treatment of coeliac disease?

    <p>It reduces the intestinal permeability of gluten-sensitive patients</p> Signup and view all the answers

    What is the significance of the characterisation of Th1 and Th17 driven IFN- and IL-17A-driven inflammation in coeliac disease?

    <p>It distinguishes CeD gluten sensitivity from other gluten-related disorders</p> Signup and view all the answers

    What is the primary goal of developing treatments to support the gluten-free diet in coeliac disease?

    <p>To assist safe gluten consumption and improve GFD adherence</p> Signup and view all the answers

    What is the consequence of false beliefs of GFD non-adherence in coeliac disease patients?

    <p>Conflict between the patient and their healthcare provider</p> Signup and view all the answers

    What is the estimated percentage of CeD diagnosed patients who achieve significant mucosal healing with a strict gluten-free diet?

    <p>Around 2%</p> Signup and view all the answers

    What is the potential benefit of inducing gluten-tolerance through gluten-oral delivery in coeliac disease patients?

    <p>It may be considered for subjects who do not want preventive treatments</p> Signup and view all the answers

    What is the primary challenge in managing coeliac disease?

    <p>The emotional, social, financial, physical, and psychological impact of a gluten-free diet</p> Signup and view all the answers

    What is the primary goal of educating patients with coeliac disease about their medications?

    <p>To improve adherence to medications</p> Signup and view all the answers

    What is the significance of HLA-DQ2 and HLA-DQ8 in coeliac disease?

    <p>They are associated with an increased risk of developing the disease</p> Signup and view all the answers

    What is the primary advantage of using pharmacological treatments in coeliac disease?

    <p>They can expand therapeutic opportunities for patients with CeD</p> Signup and view all the answers

    Study Notes

    Coeliac Disease (CD)

    • CD is a chronic immune-mediated systemic disease triggered by gluten and related prolamins in genetically susceptible individuals.
    • The only effective treatment available is a strict lifelong gluten-free diet (GFD), which can be difficult to adhere to and may lead to nutritional deficiencies.
    • Non-adherence to a GFD is estimated to be as high as 50%, particularly among adolescents and young adults.

    Definition and Prevalence

    • CD is a multifactorial illness triggered by a genetically predisposed environment in relation to gluten ingestion.
    • The cumulative risk of CD up to the age of 15 is augmented by more than 10-fold when at least one HLA risk allele is present.
    • 95-97% of coeliac patients possess DQ2, and the rest exhibit DQ8.
    • The prevalence of CD in the general population ranges between 0.1 and 1% in countries such as Spain, France, Italy, and Finland.

    Pathophysiology and Clinical Manifestations

    • CD is a complex immune-mediated enteropathy that can occur in genetically predisposed people of all ages after ingesting gluten.
    • Gluten intake leads to an immune response in the small bowel of CD patients, resulting in small intestinal inflammation.
    • The clinical presentation of CD has evolved over the past few decades, with a trend towards an increased symptomatic prevalence and the observation of non-classical or subclinical phenotypes.

    Current Management Guidelines

    • The only current treatment for CD is a strict gluten-free diet, which can be a source of anxiety and depression.
    • Life-long adherence to a gluten-free diet is necessary, and regular contact with a dietitian can provide ongoing support and improve quality of life.
    • Even small amounts of gluten (20mg per day) can cause an immune response and further damage to the intestine.

    Pharmacological Interventions

    • There is a need for non-dietary treatments for CD, as the current gluten-free diet is not always effective or easy to follow.
    • Novel approaches to gluten intolerance include preventing the immune response to gluten, rather than breaking down the gluten itself.
    • Biologics, such as monoclonal antibodies, and local anti-cytokine therapy are potential avenues for treating CD.
    • Therapies that target multiple pathways within the immune response may be required to treat CD.

    Enzyme Supplements

    • Enzyme supplements, such as prolyl endopeptidases (PEPs), can break down gluten into smaller, non-immunogenic peptides.
    • The inhibitory effect of PPIs on common PEPs is a concern, and dosage frequency and form are important factors to consider.

    Immunosuppressive Agents

    • Immunosuppressive agents, such as azathioprine or methotrexate, may be used in patients with refractory CD, but they can have significant side effects.

    Novel Therapeutic Approaches

    • ALV003, a 6-mer peptide, has been shown to degrade gluten and reduce the immune response to gluten.
    • Larazotide acetate, a mucolytic enzyme, is currently being investigated in phase II trials.
    • Atvaercept, a mixed IL-2/IL-15 antagonist, has been shown to improve histological and serological duodenal lesions in a phase 1 trial.

    Glutenase Enzymes

    • Glutenase enzymes can be used to break down gluten into smaller, non-immunogenic peptides.
    • The currently evaluated dosage of glutenase enzymes varies from 0.4 to 50 AU per gram of gluten ingested.
    • Synthetic work is ongoing to optimize the therapeutic effect of glutenase enzymes.### Clinical Trials and Enzyme Formulations
    • Clinical trials have shown that enzyme formulations can decrease GI symptoms after gluten intake when administered together with a meal containing 11g of gluten.
    • Additional data is required, especially on the possible preferential administration of this drug in newly diagnosed celiac patients before adhering to a gluten-free diet.

    Limitations of Gluten-Free Diet

    • Celiac disease (CD) is primarily treated by a strict gluten-free diet (GFD), which is not completely effective and difficult to maintain.
    • A recent prospective study showed that 88% of CD patients do not adhere strictly to a GFD.
    • This leads to higher rates of disease persistence, relapse, and complications associated with poor response to a GFD.

    Alternative Therapeutic Strategies

    • Rational non-diet responsive strategies for CD management include the adjunctive use of specific drugs acting against gluten, parallel to an incomplete compliance to a GFD.
    • Pancreatic proteases and glutenases enzymes have been tested for gluten breakdown and could be included in formulations to improve gluten hydrolysis in the gastrointestinal tract.

    Vaccine Development

    • Molecules like ZED1227, a small molecular mass inhibitor of transglutaminase-2, can block the amplification step of the gluten immune response.
    • Alternative therapeutic strategies include immune modulation, such as Treg induction or local secretory IgA induction, to dampen the local intestinal immune response.
    • Treatments based on supporting epithelial barrier integrity and decreasing gut inflammation are also being explored.

    Gluten Neutralization

    • Gluten neutralization is an alternative therapeutic strategy that involves the "enzymatic break down" of gluten peptides in the gut that are resistant to gastric and pancreatic digestion.
    • Several research groups are developing mixtures of proteolytic enzymes to destroy deamidation potential and/or T-cell stimulating epitopes in the gut.

    Clinical Trials and Evidence-Based Medicine

    • Novel targets for drug discovery in celiac disease include enzyme therapy, amylase/trypsin inhibitor, and FasL inhibitor, among others.
    • Clinical trials are ongoing to evaluate the efficacy and safety of these novel therapies.

    Novel Nondietary Therapies for Celiac Disease

    • Patients with celiac disease must maintain a stringent lifetime gluten-free diet, but additional treatment options are needed.
    • Recently, the focus has shifted towards immunological, regulatory, and epithelial targets, which may yield more specific and less toxic treatments.
    • Several novel therapies have shown promise in clinical trials, including vilazodone, larazotide acetate, and anti-IL-15 antibodies.

    Outcome Measures in Coeliac Disease Trials

    • Patients with coeliac disease suffer from ongoing symptoms and slow and incomplete mucosal healing during a gluten-free diet.
    • Alternative treatments are needed, and a large number of potential targets for treatments have been identified.
    • Outcome measures in CD therapeutic trials have been summarized by a recent study and expert-based recommendations, including patient perspectives.

    Future Directions in Celiac Disease

    • In 2016, a study demonstrated that colorectal T lymphocytes can be selectively eliminated using the humanized monoclonal antibody anti-CD3 visilizumab, inducing remission in 45% of patients with operative anemia who failed to respond to a gluten-free diet.
    • Another promising therapeutic approach is to reduce the specific inflammatory response to gluten-derived peptides.
    • Silencing genes that encode HLA-DQ2 and HLA-DQ8 using small inhibitory RNA may be a viable approach.
    • Monoclonal antibodies that inhibit the traffic of mucosal T cells exposed to gluten-derived peptides, such as natalizumab, may be helpful in treating refractory celiac disease.
    • Other drugs being explored include vedolizumab, rebrocholimab, and cilengitide.

    Patient Education and Adherence

    • Not all celiac patients find dietary compliance to be simple to achieve due to complexities such as identifying gluten-containing components in food packaging, dining out, and socializing.
    • Dietitians receive favorable overall assessments for providing dietary advice to patients.
    • Celiac disease is a systemic disorder triggered by gluten ingestion in genetically susceptible individuals and is more frequent than formerly believed.
    • The only successful therapy for celiac disease is a gluten-free diet, which excludes wheat, rye, and barley.

    Importance of Education and Counseling

    • Physicians should properly educate and counsel patients to ensure compliance with medications and prevent drug-nutrient interactions, adverse reactions, and side effects.
    • Patients' education and counseling are crucial when prescribing medications to improve adherence and prevent long-term use of certain drugs.
    • Pharmacotherapy for celiac disease involves the use of systemic or topical medicinal substances to prevent, ameliorate, or cure part of the disease or its symptoms as an adjunct to a gluten-free diet and vitamin and mineral supplementation.

    Strategies for Improving Adherence

    • New therapeutic targets have been identified, including the characterisation of Th1 and Th17 driven IFN- and IL-17A-driven inflammation.
    • Targeting Zonulin receptor (ZOT-R) has a compelling biological rationale and has led to a recent large phase IIa trial with a micronutrient conjugated, ZOT-R-inactivating monoclonal antibody.
    • Technologies designed to assist safe gluten consumption, including advice, smartphone applications, monitoring devices, shared care packages, meal plans, and dietary aids, can help educate patients and improve GFD adherence.
    • A strict, lifelong gluten-free diet is the cornerstone of managing celiac disease, but it is difficult to adhere to, with around 50% of patients having dietary transgressions during the preceding 6-12 months.

    Conclusion and Future Perspectives

    • The recent development of innovative drugs is expanding therapeutic opportunities for patients with celiac disease.
    • The need to supplement GFD for persistent CD has resulted in the design of pharmacotherapy strategies differently from those devised for CD prevention.
    • Treatment with anti-Zonulin is a genuine new strategy that targets the increased intestinal permeability of gluten-sensitive patients.
    • The new induction of gluten-tolerance by gluten-oral delivery is a novel approach that may be considered for subjects who do not want preventive treatments but look for protection and eventual cure.

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