New Pharmacological Therapies for Celiac Disease – A Systematic Review

Background: Celiac disease is an immune-mediated condition caused by gluten in genetically susceptible individuals. Although a gluten-free diet is the basis of treatment, it is often difficult to maintain and may not fully prevent symptoms or intestinal damage. Objective: This systematic review examines emerging non-dietary therapies for celiac disease, with emphasis on their mechanisms, clinical effectiveness, and safety. Methods: A total of 23 peer-reviewed studies were analyzed, covering enzyme therapies, gluten sequestrants, tight junction modulators, immunotherapies, cytokine inhibitors, transglutaminase blockers, and probiotics. Results: TAK-062 and ZED1227 emerged as the most promising candidates. TAK-062 showed strong gluten-degrading activity, while ZED1227 consistently reduced mucosal injury. Other enzymes, like latiglutenase, offered partial benefit, especially in seropositive patients. BL-7010 sequestered gliadin effectively in preclinical models. Larazotide acetate improved symptoms at low doses. Immunotherapies showed mixed outcomes—Nexvax2 failed in phase 2, while TAK-101 showed early potential. AMG 714 helped in refractory cases but lacked strong histological effects. Probiotics improved gut symptoms and microbiota balance, supporting their role as adjuncts. Conclusions: While most therapies remain investigational, several show real potential as supplements to the gluten-free diet. Future research should focus on long-term outcomes and personalized approaches to improve disease management.