Advances in celiac disease research and care could soon reshape how patients are diagnosed, monitored, and treated, Dan Leffler, MD, MS, AGAF, said during the keynote address at a virtual policy symposium hosted by the Society for the Study of Celiac Disease and the Celiac Disease Foundation.
“We are really in an exciting transitional period in celiac disease,” said Dr. Leffler, executive medical director and global program lead for celiac disease at Chugai Pharmaceuticals and associate professor of medicine at Harvard Medical School. “A lot of pieces are coming together. The celiac population is growing and is poised to grow even further. Limitations of the gluten-free diet are increasingly clear. Therapies and new diagnoses are coming.”
Opening the session, Dawn Adams, MD, MS, CNSC, a gastroenterologist at Vanderbilt University Medical Center and president of the Society for the Study of Celiac Disease, emphasized the need for alternatives to the gluten-free diet. She described celiac disease as a condition in which “for some, the burden of treatment is actually greater than the benefits of treating the disease.” She said ongoing discussions among experts are essential to ensure that future therapies can benefit a broad range of patients rather than only narrowly defined subgroups.
Dr. Leffler noted that celiac disease affects roughly 1% of the global population and carries substantial clinical, psychosocial, and economic consequences. In addition to facing an increased risk of death and several serious comorbidities, patients must manage the daily challenges of adhering to a strict gluten-free diet.
As celiac disease prevalence continues to rise, Dr. Leffler pointed to the emergence of population-based screening efforts in the United States and Europe as an encouraging development. “Celiac disease screening programs, after years and years of discussion, are really beginning in the US and Europe,” he said. “I believe this has the potential to result in the biggest increase in celiac disease diagnosis since tTG [tissue transglutaminase] testing became widely available.”
Population-based screening efforts could greatly increase the number of patients diagnosed with celiac disease and referred to gastroenterology practices, Dr. Leffler said. But diagnosing the condition remains a challenge. Many adults wait six to 10 years for a diagnosis, he said, and are often given other diagnoses first, such as irritable bowel syndrome, food sensitivities, eating disorders, or stress-related conditions. Even today, he noted, fewer than half of people with celiac disease in the United States have been diagnosed.
Dr. Leffler also challenged the belief that most patients do well on a gluten-free diet alone. Citing a recent survey of 2,001 Americans with biopsy-confirmed celiac disease who had followed a gluten-free diet for at least 12 months, he said that 85% reported experiencing gluten-related symptoms at least once during the previous three months.
“What was really impressive, and even to me somewhat shocking, was the amount of functional impairment that these gluten exposures caused,” Dr. Leffler said. “About 75% of them experienced life impacts, such as missing work, school, reduced work function, for at least a couple days.”
Those findings underscore the substantial societal burden of accidental gluten exposure, Dr. Leffler said.
“If you imagine that most people are getting exposed to gluten every month or every couple months from this survey, and most of those are having at least a few days of reduced ability to work or go to school, this actually becomes a significant impact on the patients, on their families, on society in general,” he said.
Patients are increasingly interested in treatment options beyond simply avoiding gluten, Dr. Leffler said. Surveys he cited show that about 90% of patients would like a therapy that could either replace or be used alongside a gluten-free diet. Most patients aren't looking to eat gluten freely, he said, but rather want protection against accidental gluten exposure.
Researchers have also gained a better understanding of the wide range of experiences among people with celiac disease.
“We used to just think about celiac disease as one disease, and you put everyone on a diet,” Dr. Leffler said. “We now recognize it's really a spectrum of patients and their response to celiac disease and response to gluten-free diet.”
One advantage for drug developers, he continued, is that celiac disease is one of the most thoroughly understood immune-related disorders. Researchers have a clear picture of how the disease develops, from the way gluten is processed in the body to the immune reactions that damage the intestine. This deeper understanding has fueled the development of a wide range of potential therapies.
Although larazotide acetate and other promising agents have failed to reach approval, Dr. Leffler said the field has learned valuable lessons about trial design.
“Celiac disease is not inflammatory bowel disease, and trial design cannot be assumed to be similar,” he said. Investigators have also learned that symptoms do not necessarily reflect active celiac disease, that patients alter their behavior when enrolled in clinical trials, and that histologic damage correlates poorly with symptom severity.
Beyond therapeutics, Dr. Leffler pointed to advances in gluten immunogenic peptide testing, proteomic and transcriptomic assessment of intestinal injury, cytokine-based diagnostic approaches, and population-management tools derived from real-world and electronic medical record data.
Still, he cautioned that realizing the promise of these innovations will require coordination among clinicians, researchers, regulators, payers, patient advocates, and patients themselves.
“We need different stakeholders coming together early and often if we're going to realize the potential new developments and really build a better future for everyone with celiac disease,” Dr. Leffler said.
Dr. Leffler is a board member of the Foundation for Celiac Disease Outcome Measures.