Reset after RESET: insights from a negative trial in coeliac disease

The only current treatment for coeliac disease is a strict gluten-free diet for life. Although effective in many, a proportion of patients will remain symptomatic or have ongoing small intestinal inflammation, despite adhering to a gluten-free diet. 1 Kivelä L Caminero A Leffler DA Pinto-Sanchez MI Tye-Din JA Lindfors K Current and emerging therapies for coeliac disease. Nat Rev Gastroenterol Hepatol. 2021; 18: 181-195 Crossref PubMed Scopus (46) Google Scholar Gluten can be detected in the stool of the most patients with coeliac disease on a gluten-free diet, suggesting that inadvertent contamination is frequent. 2 Stefanolo JP Tálamo M Dodds S et al. Real-world gluten exposure in patients with celiac disease on gluten-free diets, determined from gliadin immunogenic peptides in urine and fecal samples. Clin Gastroenterol Hepatol. 2021; 19: 484-491 Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar Gluten-free alternatives are costly and not readily available everywhere. Thus, there is a growing interest in developing adjuvant therapies for coeliac disease. Because coeliac disease is driven by pathogenic gluten-specific CD4+ T cells, modulation of this pathway has long been sought. Although difficult to achieve, this approach would be highly desirable because it targets the key immune mechanism, which could revert the pathogenic process and allow consumption of the dietary disease driver, gluten. Efficacy and safety of gluten peptide-based antigen-specific immunotherapy (Nexvax2) in adults with coeliac disease after bolus exposure to gluten (RESET CeD): an interim analysis of a terminated randomised, double-blind, placebo-controlled phase 2 studyNexvax2 did not reduce acute gluten-induced symptoms. Masked bolus vital gluten challenge provides an alternative to extended gluten challenge in efficacy studies for coeliac disease. Full-Text PDF