Confronting Unmet Needs in Celiac Disease, With Joseph Murray, MD

Celiac disease is one of the most common autoimmune conditions in the world, yet it carries a distinction that sets it apart from nearly every other chronic GI disease gastroenterologists manage: there is no approved drug to treat it. While the inflammatory bowel diseases have benefited from decades of investment and a crowded therapeutic pipeline, celiac disease has largely been left behind.

At Digestive Disease Week (DDW) 2026 in Chicago, IL, Joseph Murray, MD, a gastroenterologist and professor of medicine at Mayo Clinic, outlined where the field stands on diagnosis, long-term management, and the road ahead for drug development.

A Diagnosis in Transition

For decades, celiac disease diagnosis required endoscopic biopsy of the small intestine, but that paradigm is shifting. When the tissue transglutaminase IgA (tTG-IgA) antibody test returns at > 10 times the upper limit of normal, the probability of celiac disease is high enough that a biopsy-avoidance strategy is now established practice in pediatrics and is increasingly being considered for adults.

The 2023 ACG guidelines recommend EGD with multiple duodenal biopsies for confirmation of diagnosis in both children and adults, but also suggest that in adults who are unwilling or unable to undergo endoscopy, a combination of high-level tTG-IgA exceeding 10 times the upper limit of normal with a positive endomysial antibody on a second blood sample may serve as a diagnosis of likely celiac disease. A follow-up biopsy should be considered at 2 years, given that the median time to achieve mucosal healing is 3 years.

Murray emphasized, however, that at least half of patients do not reach that serologic threshold and still require endoscopy, and timing is critical. If a patient goes gluten-free before the biopsy is performed, intestinal healing may produce a false-negative result, obscuring the diagnosis entirely.

"It's very important that as a specialty we recognize the time dependency of accurate diagnosis," Murray told HCPLive. "We want patients to get a diagnosis so they can get on treatment quickly — but they need to still be eating gluten when that biopsy is done."

Managing the Whole Patient

Murray additionally stressed that a celiac disease diagnosis should not end with dietary counseling. Newly diagnosed patients require evaluation for nutritional deficiencies, anemia, and bone density loss, which can be substantial. Referral to a dietitian with celiac-specific expertise is essential, as well as long-term gastroenterologist follow-up, including repeat serology at 6 months to confirm antibody decline and follow-up biopsy at 1 to 2 years to verify mucosal healing.

Ongoing symptoms despite a gluten-free diet should prompt evaluation for commonly associated conditions, including microscopic colitis, small intestinal bacterial overgrowth, and pancreatic exocrine insufficiency, and, in some cases, a reassessment of the original diagnosis.

"We would not discharge a patient with Crohn's disease from our care," Murray said. "It shouldn't be any different for celiac disease."

A Pipeline Finally Taking Shape

The most consequential gap in celiac disease management is pharmacologic, with no drug currently approved for the condition. Murray acknowledged the field's checkered history with drug development: roughly a dozen agents have entered clinical development, with many stumbling or failing.

The pipeline now includes more than 30 investigational agents across multiple stages of development, with active programs targeting IL-15-mediated inflammation, enzyme therapies, and immune tolerance induction. Among the more closely watched candidates is TEV-53408, an anti-IL-15 monoclonal antibody from Teva that recently received FDA Fast Track designation and is currently in phase 2 evaluation.

Murray noted that the gluten-free diet, the current standard of care in celiac disease, fails more patients than is widely appreciated. An estimated 30 to 40% do not achieve mucosal healing despite their best efforts, and a similar proportion experience significant symptoms from accidental gluten exposures.

“The gluten free diet is very easy for me to say ‘go gluten free.’ That's sounds easy, but the living of that is not easy, and it's not particularly effective,” he said. "I'm optimistic that we will have better treatments, but we have to prove that they work."

Editor's note: Murray reports no relevant disclosures.

References

1. Murray JA. DRUG DEVELOPMENT IN CELIAC DISEASE: HOW CAN WE GET FROM THE LAB TO CLINIC? Session presented at: Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

2. Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2023;118(1):59-76. doi:10.14309/ajg.0000000000002075

3. Teva. Teva Celiac Disease Candidate Granted Fast Track Designation by US FDA. May 27, 2025. Accessed May 3, 2026. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Teva-Celiac-Disease-Candidate-Granted-Fast-Track-Designation-by-US-FDA/default.aspx