Exploring novel therapies for coeliac disease: are safe drugs tolerable?

Abstract

Coeliac disease is the only autoimmune condition where the main environmental trigger, gluten, is known. 1 Catassi C Verdu EF Bai JC Lionetti E Coeliac disease. Lancet. 2022; 399: 2413-2426 Summary Full Text Full Text PDF PubMed Scopus (36) Google Scholar Adherence to a strict gluten-free diet for life is essential for intestinal mucosal recovery, alleviation of symptoms, and to reduce the risk of complications such as anaemia, osteoporotic fractures, and small bowel cancer. 2 Kivelä L Caminero A Leffler DA et al. Current and emerging therapies for coeliac disease. Nat Rev Gastroenterol Hepatol. 2020; 18: 1-15 Google Scholar However, strict long-term compliance with a gluten-free diet can be socially inconvenient and expensive. 3 Pinto-Sanchez MI Verdu EF Gordillo MC et al. Tax-deductible provisions for gluten-free diet in Canada compared with systems for gluten-free diet coverage available in various countries. Can J Gastroenterol Hepatol. 2015; 29: 104-110 Crossref PubMed Scopus (21) Google Scholar Moreover, up to 30% of people with coeliac disease continue to have symptoms despite attempting the strict diet 4 Penny HA Baggus EMR Rej A et al. Non-responsive coeliac disease: a comprehensive review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients. 2020; 12: 216 Crossref PubMed Scopus (43) Google Scholar , and almost 80% indicated a desire for therapy to liberalise their diet. 5 De Leon Morilla D Ventoso M Lebovits J et al. Patients' risk tolerance for non-dietary therapies in celiac disease. Clin Gastroenterol Hepatol. 2022; 20: 2647-2649 Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Therefore, emerging therapies to support the gluten-free diet, including those targeting induction of tolerogenic mechanisms, are currently being investigated in clinical trials. 6 Pinto-Sanchez MI Silvester JA Lebwohl B et al. Society for the Study of Celiac Disease position statement on gaps and opportunities in coeliac disease. Nat Rev Gastroenterol Hepatol. 2021; 18: 875-884 Crossref PubMed Scopus (13) Google Scholar Safety and tolerability of KAN-101, a liver-targeted immune tolerance therapy, in patients with coeliac disease (ACeD): a phase 1 trialKAN-101 has an acceptable safety profile in patients with coeliac disease with no dose-limiting toxicities and no maximum tolerated dose was observed. Rapid systemic clearance of KAN-101 was observed and no accumulation on repeated dosing. A future study will evaluate the safety and efficacy, including biomarker responses with a gluten challenge, of KAN-101 at doses 0·6 mg/kg and greater in patients with coeliac disease. Full-Text PDF