Current and emerging therapies for coeliac disease

Coeliac disease is a common enteropathy that occurs in genetically susceptible individuals in response to the ingestion of gluten proteins present in wheat, rye and barley. Currently, the only available treatment for the condition is a strict, life-long gluten-free diet that, despite being safe and often effective, is associated with several challenges. Due to the high cost, particularly restrictive nature and perception of decreased quality of life associated with the diet, some patients are continuously exposed to gluten, which prevents an adequate disease control. Moreover, a subgroup of patients does not respond to the diet adequately, and healing of the small-bowel mucosa can be incomplete. Thus, there is a need for alternative treatment forms. The increasingly understood pathogenetic process of coeliac disease has enabled the identification of various targets for future therapies. Multiple investigational therapies ranging from tolerogenic to immunological approaches are in the pipeline, and several drug candidates have entered phase II/III clinical trials. This Review gives a broad overview of the different investigative treatment modalities for coeliac disease and summarizes the latest advances in this field. A gluten-free diet is currently the only effective treatment for coeliac disease but an increased understanding of disease pathogenesis has led to the identification of several potential therapeutic targets. This Review provides a broad overview of current and emerging therapies for coeliac disease. Key points At present, a gluten-free diet is the only effective treatment for coeliac disease but is associated with several possible challenges, including a high economic and societal burden, inferior quality of life and sometimes inadequate response. An increased understanding of the pathogenetic process in coeliac disease has revealed various therapeutic targets for future drugs that could complement or replace a gluten-free diet. Novel therapeutic strategies include approaches to detoxify gluten already in the gastrointestinal tract by sequestrants or peptidases. Other investigational approaches comprise blocking intestinal epithelial permeability or the enzymatic activity of transglutaminase 2. Restoring immune tolerance to gluten or targeting the gluten-induced immune activation has also been investigated as possible therapeutic options. The most advanced drug candidates have now entered phase III clinical trials.