Research Round-Up 2023
The Celiac Disease Foundation is pleased to have presented original research at multiple events during fall 2023, including the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) Annual Meeting and United European Gastroenterology Week (UEGW). Coming up in November, the Foundation will also present at the Association of European Coeliac Societies (AOECS) General Assembly. The research – co-authored by Chief Executive Officer Marilyn Geller in partnership with Takeda and Adelphi Real World – describes the patient experience with celiac disease and highlights the need for better therapies and physician management of the disease.
Takeda’s Virtual Celiac Symptoms Study (VCSS) aimed to understand celiac disease (CeD) symptoms and impacts and help identify patient groups who may need additional treatment beyond a gluten-free diet (GFD). The VCSS observational study was conducted in the United States among adults and adolescents with CeD from July 25, 2022, to March 4, 2023, recruited by the Celiac Disease Foundation. Participants were asked to complete daily, weekly, and monthly questionnaires about their symptoms and quality of life for a period of 12 weeks using a smartphone app. The Foundation and Takeda shared abstracts of the study broken down by adolescent and adult cohorts at baseline and reported symptoms over 12 weeks.
Adelphi Real World’s two surveys – Diagnosing Celiac Disease in the United States of America, Germany, Italy, and Spain: Findings from a Real-World Survey and Physician Management of Celiac Disease: A Comparison of Disease Knowledge, Diagnosis, and Patient Management between Gastroenterologists and Primary Care Physicians in Germany, Italy, Spain, and the United States – Findings from a Real-World Survey – aimed to assess diagnosis patterns in the United States of America (USA) and Europe. The studies also sought to understand differences in disease knowledge and approaches to the diagnosis and management of patients with celiac disease between gastroenterologists (GIs) and primary care physicians (PCPs), respectively. The two studies were conducted using the Adelphi CeD Disease Specific Programme™, a real-world cross-sectional survey with sections of retrospective data collection of physicians and their CeD patients between July 2021 and January 2022.
NASPGHAN Annual Meeting
The North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN), held its annual meeting in October in San Diego, California. Summaries of what the Celiac Disease Foundation presented:
The Virtual Celiac Symptoms Study: Symptom and gluten-free diet perceptions of adolescents at baseline
What did they do?
The goal of this study was to characterize the symptom patterns and gluten-free diet (GFD) adherence in adolescents with celiac disease (CeD) through a prospective observational study (Virtual Celiac Symptoms Study: VCSS). Researchers describe the self-reported symptom patterns and GFD adherence at the time of enrollment in the VCSS. The results of the study focused on adolescent participants’ perceptions of their disease experience.
What did they find?
Despite following a gluten-free diet, patients still experienced symptoms related to CeD, particularly after accidental gluten exposure, and over 54% of adolescent participants were extremely likely to develop CeD symptoms after gluten exposure. The most commonly reported symptoms were abdominal pain, tiredness, bloating, and diarrhea. The most bothersome symptoms were abdominal pain, nausea, diarrhea, and brain fog. Anxiety and depression were the most common comorbidities among adolescent participants, regardless of disease severity.
What does this mean? What does this change?
The study emphasizes the importance of gaining a deeper understanding of the reasons why adolescent patients continue to experience CeD symptoms despite adhering to a GFD. It also highlights the need for better comprehension of CeD symptoms in adolescents following a GFD and the development of additional treatment options for this patient group.
The Virtual Celiac Symptoms Study: Reported symptoms over 12 weeks in adolescents
What did they do?
The goal of this study was to assess the gluten-free diet (GFD) experience and celiac disease (CeD)-related symptoms in the adolescent population (aged 12 to under 18 years) of the VCSS over 12 weeks.
What did they find?
During the 12-week observational period, adolescent patients with CeD continued to experience gastrointestinal symptoms despite following a gluten-free diet – with the core CeD symptoms of tiredness, abdominal pain, and bloating having the highest number of days with symptom occurrence. The average number of days with reported gluten exposure was almost 7 days and the average days of reported symptoms was about 50, over the 12-week study period. All participants reported at least one core CeD symptom and each GI symptom occurred at least once in over 80% of adolescent participants (apart from diarrhea in those who reported following a GFD).
What does this mean? What does this change?
It’s important to distinguish between symptoms caused by gluten exposure and those that aren’t, and to find effective treatments for managing CeD in patients who follow a GFD; the study’s findings highlight this need. Furthermore, the symptom patterns found in this study suggest that specific gastrointestinal symptoms should be considered as relevant endpoints in future research of potential medications for CeD. The indicators of a clinical trial’s success are known as endpoints. These endpoints show whether the treatment was effective in curing or controlling the disease progression.
Other notable presentations
Is AI the future of Pediatric Celiac Disease Diagnosis?
Dr. Imad Absah, MD, pediatric gastroenterologist at Mayo Clinic Children’s Center, shared how an artificial intelligence-based algorithm helped accurately identify pediatric patients with known CeD who had not received suitable follow-up care. This tool aims to improve the detection and management of CeD in children. The use of this tool could potentially lead to better health outcomes for children.
Zonulin: A Promising Celiac Disease Biomarker
Dr. Maureen Leonard, MD, MMSc, clinical director of the Center for Celiac Research & Treatment at Massachusetts General Hospital for Children and the Foundation’s 2023 Young Investigator in Clinical Science prize laureate, presented new research findings that suggest multiple courses of antibiotics could affect the levels of zonulin (a protein that helps to control what substances can pass through the intestinal walls) in the body. Zonulin could be a biomarker for early detection of CeD and may also help us understand why taking antibiotics could increase the risk of CeD in children. The abstract presented at NASPGHAN showed that significantly increased levels of zonulin in infants and toddlers were associated with CeD diagnosis. Watch Dr. Leonard’s HCP Live Gastroenterology video to learn more.
A Push for Standardizing Celiac Disease Diagnosis
A new study presented by Dr. Denis Chang, MD, pediatric gastroenterologist at Boston Children’s Hospital, is set to observe the frequency of biopsies in children who are at high risk of CeD based on their blood tests. The study aims to determine the number of children who meet the criteria for non-biopsy diagnoses based on the European standard. Dr. Chang was a speaker at this year’s Celiac Smarts Symposium co-sponsored by the Celiac Disease Foundation.
Watch Dr. Chang’s interview with HCP Live Gastroenterology to learn more.
Dr. Leonard and Dr. Absah were both honored as newly-elected co-Chairs and Dr. Chang as a co-Vice Chair of the NASPGHAN Celiac Disease Special Interest Group (SIG) at the Celiac Disease Foundation’s SIG dinner before the conference.
UEGW
United European Gastroenterology, the leading non-profit organization for excellence in digestive health in Europe, kicked off its hybrid UEG Week (UEGW) and Postgraduate Teaching (PGT) experiences in October in Copenhagen. Summaries of what the Celiac Disease Foundation and partners presented:
The Virtual Celiac Symptoms Study: symptom and gluten-free diet perception at baseline
Encore from Digestive Disease Week (DDW) 2023
What did they do?
The study collected data from patients for 12 weeks, using a smartphone app. Participants answered daily and weekly questionnaires for a period of 12 weeks, sharing their symptoms and information about their quality of life. All participants were 18 years old or older for the adult cohort. The goal of this study was to describe the baseline disease characteristics of the adult study population of the Virtual Celiac Symptoms Study (VCSS). Researchers aimed to provide clear information about celiac disease (CeD) and its effects on the study population.
What did they find?
Although all patients stated they were following a gluten-free diet (GFD), almost 60% experienced symptoms related to CeD in the week before completing the questionnaire. Bloating, tiredness, abdominal pain, and diarrhea were the most reported symptoms. Notably, the most bothersome symptoms were diarrhea, abdominal pain, brain fog, and nausea. Almost all patients (96.4%) who were surveyed reported experiencing symptoms of CeD. Surprisingly, a quarter of those patients experienced symptoms despite not knowingly consuming gluten. In total, 84% of patients reported experiencing CeD symptoms after gluten exposure. Over the course of the study’s past year, 11% of patients reported being hospitalized or visiting the emergency room due to CeD symptoms.
What does this mean? What does this change?
More needs to be done to understand and treat ongoing symptoms in individuals with CeD who are following a GFD. Patients with CeD on a GFD need new and better treatment options. Even though this represents only an initial analysis of the adult population, this study provides clear evidence that a GFD may not be sufficient to manage CeD-related symptoms and highlights the need for alternative therapies. Additional analysis will provide a better understanding of the disease experience for both adults and adolescents.
The Virtual Celiac Symptoms Study: Reported symptoms over 12 weeks in adults
What did they do?
The goal of this study is to assess the gluten-free diet (GFD) experience and celiac disease (CeD)-related symptoms in the adult population of the Virtual Celiac Symptoms Study (VCSS) over 12 weeks. The study collected data from patients using a smartphone app, where participants answered daily and weekly questionnaires for a period of 12 weeks, sharing their symptoms and quality of life. All participants were 18 years old or older for the adult cohort.
What did they find?
Almost 88% of participants identified as female and almost all participants reported to be White. Most (71%) of adult patients reported having moderate or severe symptoms at the beginning of the study. The average number of days of reported symptoms was 60.3. Tiredness, bloating, and abdominal pain were the most frequently reported symptoms during the 12-week study period. All adult participants reported at least one core CeD symptom. Each gastrointestinal (GI) symptom, except for nausea and vomiting, occurred at least once in over 90% of adult participants.
What does this mean? What does this change?
Despite sticking to a GFD, patients with CeD continue to experience GI symptoms, regardless of the level of adherence or irritable bowel syndrome diagnosis. The study suggests that clinical trials evaluating potential therapies for CeD may benefit from including GI symptoms such as diarrhea, nausea, bloating, and abdominal pain as important co-endpoints (targeted outcomes of a clinical trial that are used to help determine the success and safety of the therapy being studied), to help assess the effectiveness of treatments. More studies are needed to better understand CeD and develop more treatment options for people who follow a GFD.
AOECS
The Association of European Coeliac Societies (AOECS) will host its 35th General Assembly Conference on November 3 in Athens, Greece. As the North American affiliate member, the Celiac Disease Foundation will be presenting four studies presented at the DDW, NASPGHAN, and UEGW meetings.
Studies presented earlier
- The Virtual Celiac Symptoms Study: Reported symptoms over 12 weeks in adults (see summary above under UEGW section)
- The Virtual Celiac Symptoms Study: Reported Symptoms over 12 weeks in adolescents (see summary above under NASPGHAN section)
Diagnosing Celiac Disease in the United States of America, Germany, Italy and Spain: Findings from a Real-World Survey
The study collected data using the Adelphi CeD Disease Specific Programme, a survey conducted in the United States of America, Germany, Italy, and Spain between July 2021 and January 2022. After the start of the study, doctors completed record forms for their next 8 consulting adult patients with celiac disease (CeD) who had symptoms in the last year. The forms recorded instances where the diagnosis was delayed or incorrect, and any diagnostic tests that were given. The same patients were invited to complete a patient self-completion form capturing consultation history and awareness of CeD prior to diagnosis.
What did they find?
The study included 2,244 CeD patients with an average age of 36.7, with over half of the patients female. Most patients waited 3-6 months before seeing a doctor after experiencing symptoms. The shortest waiting time was in Germany. The main reason for this delay was that patients tended to wait to see if their symptoms would go away on their own. In the USA, 71% of patients waited, in Germany 85%, in Italy 63%, and in Spain 61%. Patients experienced a delay of 1-3 months from the initial consultation to diagnosis, mainly due to waiting for tests. More than one-third of patients were initially misdiagnosed, with irritable bowel syndrome being the most common misdiagnosis in the USA (84%). The reason for diagnosis varied for each country, but symptom presentation was the most common overall. The level of CeD screening was higher in Italy than in all other countries and all diagnostic tests were used less in the USA in comparison to the other countries.
What does this mean? What does this change?
The study revealed that patients in the USA, Germany, Italy, and Spain experienced long delays in their diagnosis of CeD and were often misdiagnosed. More research is needed to determine how delayed diagnosis affected the health of individuals with CeD. This will help the research community better understand further health problems and negative patient outcomes.
Physician Management of Celiac Disease: A Comparison of Disease Knowledge, Diagnosis, and Patient Management between Gastroenterologists and Primary Care Physicians in Germany, Italy, Spain, and the United States – Findings from a Real-World Survey
The study collected data using the Adelphi CeD Disease Specific Programme, a survey conducted in the United States of America, Germany, Italy, and Spain between July 2021 and January 2022. Doctors completed a survey to measure opinions and perceptions about their treatment practices, diagnostic and celiac disease (CeD) monitoring practices, and other factors. The doctors were separated into two groups: gastroenterologists (GIs) and primary care physicians (PCPs).
What did they find?
The study included 278 doctors from Germany, Italy, Spain, and the USA. Of these, 178 specialized in gastrointestinal issues, and 100 were PCPs. The results showed that gastrointestinal specialists used biopsies, blood tests, and imaging tests more often than PCPs did when diagnosing patients. The same trend was observed for monitoring tests. GIs and PCPs have different levels of knowledge and understanding about CeD. It was found that PCPs were less informed about whether villus atrophy (damage on the villi, small fingerlike projections that line the small intestine, that promote nutrient absorption), which is a common symptom of CeD, can be reversed in patients compared to GIs. GIs were also more likely to consider villus atrophy when evaluating disease severity, progression, and remission status. There were also differences in opinion on the safe level of gluten intake for patients with CeD, with more GIs stating that there is no safe level compared to PCPs. Additionally, some PCPs were unsure if gluten intake is acceptable for non-symptomatic patients. Despite these disparities, both GIs and PCPs agreed that increased awareness and education for PCPs is key to early diagnosis of CeD.
What does this mean? What does this change?
PCPs and GIs differ in their diagnosis and management of CeD. This study found that PCPs have a significant knowledge gap regarding CeD, which may lead to inconsistent care for patients. Therefore, there is a need for further medical education to improve the consistency of care for patients with CeD.