Investigational drug therapies for coeliac disease – where to from here?

References

• Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut. June 2014. DOI:10.1136/gutjnl-2013-306578.
   Web of Science ®Google Scholar
• Lohi S, Mustalahti K, Kaukinen K, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther. 2007;26:1217–1225. DOI:10.1111/j.1365-2036.2007.03502.x.
   PubMed Web of Science ®Google Scholar
• O’Leary C, Wieneke P, Healy M, et al. Celiac disease and the transition from childhood to adulthood: a 28-year follow-up. Am J Gastroenterol. 2004;99:2437–2441.
   PubMed Web of Science ®Google Scholar
• Olsson C, Lyon P, Hörnell A, et al. Food that makes you different: the stigma experienced by adolescents with celiac disease. Qual Health Res. 2009;19:976–984.
   PubMed Web of Science ®Google Scholar
• Green PHR, Cellier C. Celiac disease. N Engl J Med. 2007;357:1731–1743.
   PubMed Web of Science ®Google Scholar
• Kupfer SS, Jabri B. Pathophysiology of celiac disease. Gastrointest Endosc Clin N Am. 2012;22:639–660.
   PubMedGoogle Scholar
• Barker JM, Jennifer M, Barker EL, et al. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 2008;55:349–365.
   PubMedGoogle Scholar
• Jabri B, Sollid LM. Mechanisms of disease: immunopathogenesis of celiac disease. Nat Clin Pract Gastroenterol Hepatol. 2006;3:516–525.
   PubMedGoogle Scholar
• Kaukinen K, Lindfors K, Mäki M. Advances in the treatment of coeliac disease: an immunopathogenic perspective. Nat Rev Gastroenterol Hepatol. 2013;11:36–44.
   PubMed Web of Science ®Google Scholar
• Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Endoscopy. 1993;105:910–922.
   Google Scholar
• Rosén A, Sandström O, Carlsson A, et al. Usefulness of symptoms to screen for celiac disease. Pediatrics. 2014;133:211–218. DOI:10.1542/peds.2012-3765.
   PubMed Web of Science ®Google Scholar
• Dewar DH. Celiac disease: management of persistent symptoms in patients on a gluten-free diet. WJG. 2012;18:1348.
   PubMed Web of Science ®Google Scholar
• Fera T, Cascio B, Angelini G, et al. Affective disorders and quality of life in adult coeliac disease patients on a gluten-free diet. Eur J Gastroenterol Hepatol. 2003;15:1287.
   PubMed Web of Science ®Google Scholar
• Lee A, Newman JM. Celiac diet: its impact on quality of life. J Am Diet Assoc. 2003;103:1533–1535.
   PubMed Web of Science ®Google Scholar
• Peräaho M, Kaukinen K, Mustalahti K, et al. Effect of an oats‐containing gluten‐free diet on symptoms and quality of life in coeliac disease. A randomized study. Scand J Gastroenterol. 2009;39:27–31.
   Google Scholar
• Mustalahti K, Lohiniemi S, Collin P, et al. Gluten-free diet and quality of life in patients with screen-detected celiac disease. Eff Clin Pract. 2002;5:105–113.
   PubMedGoogle Scholar
• Wacklin P, Laurikka P, Lindfors K, et al. Altered duodenal microbiota composition in celiac disease patients suffering from persistent symptoms on a long-term gluten-free diet. Am J Gastroenterol. 2014;109:1933–1941.
   PubMed Web of Science ®Google Scholar
• Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015;12:497–506.
   PubMed Web of Science ®Google Scholar
• Hall NJ, Rubin G, Charnock A. Systematic review: adherence to a gluten-free diet in adult patients with coeliac disease. Aliment Pharmacol Ther. 2009;30:315–330. DOI:10.1111/j.1365-2036.2009.04053.x.
   PubMed Web of Science ®Google Scholar
• Bardella MT, Velio P, Cesana BM, et al. Coeliac disease: a histological follow-up study. Histopathology. 2007;50:465–471.
   PubMed Web of Science ®Google Scholar
• Kaukinen K, Peräaho M, Lindfors K, et al. Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease. Aliment Pharmacol Ther. 2007;25:1237–1245.
   PubMed Web of Science ®Google Scholar
• Newnham ED, Shepherd SJ, Strauss BJ, et al. Adherence to the gluten-free diet can achieve the therapeutic goals in almost all patients with coeliac disease: a 5-year longitudinal study from diagnosis. J Gastroenterol Hepatol. 2016;31:342–349. DOI:10.1111/jgh.13060.
   PubMed Web of Science ®Google Scholar
• Leffler D, Kupfer SS, Lebwohl B, et al. Development of celiac disease therapeutics: report of the third gastroenterology regulatory endpoints and advancement of therapeutics workshop. Gastroenterology. 2016;151:407–411.
   PubMed Web of Science ®Google Scholar
• Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and mortality in coeliac disease. Aliment Pharmacol Ther. 2013;37:332–339.
   PubMed Web of Science ®Google Scholar
• Rubio-Tapia A, Rahim MW, See JA, et al. Mucosal recovery and mortality in adults with celiac disease after treatment with a gluten-free diet. Am J Gastroenterol. 2010;105:1412–1420.
   PubMed Web of Science ®Google Scholar
• Leffler DA, Dennis M, George JBE, et al. A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol. 2009;7:530–536.e532.
   PubMed Web of Science ®Google Scholar
• Comino I, Real A, Vivas S, et al. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr. 2012 January. DOI:10.3945/ajcn.111.026708.
   PubMed Web of Science ®Google Scholar
• Ryan D, Newnham ED, Prenzler PD, et al. Metabolomics as a tool for diagnosis and monitoring in coeliac disease. Metabolomics. November 2014. DOI:10.1007/s11306-014-0752-9.
   PubMed Web of Science ®Google Scholar
• Mitea C, Havenaar R, Drijfhout JW, et al. Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: implications for coeliac disease. Gut. 2007;57:25–32.
   PubMed Web of Science ®Google Scholar
• Lähdeaho M-L, Kaukinen K, Laurila K, et al. Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. Gastroenterology. 2014;146:1649–1658.
   PubMed Web of Science ®Google Scholar
• Tye-Din JA, Anderson RP, Ffrench RA, et al. The effects of ALV003 pre-digestion of gluten on immune response and symptoms in celiac disease in vivo. Clin Immunol. 2010;134:289–295. DOI:10.1016/j.clim.2009.11.001.
   PubMed Web of Science ®Google Scholar
• Murray JA, Kelly CP, Green PHR, et al. No difference between latiglutenase and placebo in reducing villous atrophy or improving symptoms in patients with symptomatic celiac disease. Endoscopy. 2017;152:787–98.e2.
   Google Scholar
• Stepniak D, Stepniak D, Spaenij-Dekking L, et al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. Am J Physiol Gastrointest Liver Physiol. 2006;291:G621–G629.
   PubMed Web of Science ®Google Scholar
• Tack GJ. Consumption of gluten with gluten-degrading enzyme by celiac patients: a pilot-study. Wjg. 2013;19:5837.
   PubMed Web of Science ®Google Scholar
• Heredia-Sandoval NG, Calderón de la Barca AM, Islas-Rubio AR. Gluten degradation in wheat flour with Aspergillus niger prolyl-endopeptidase to prepare a gluten-reduced bread supplemented with an amaranth blend. J Cereal Sci. 2016;71:73–77.
   Web of Science ®Google Scholar
• Cornell HJ, Czyzewska A, MacRae FA, et al. The effect of enzyme supplementation on symptoms and duodenal histology in celiac patients. Int J Celiac Dis. 2016;4:40–47.
   Google Scholar
• Pinier M, Verdu EF, Nasser Eddine M, et al. Polymeric binders suppress gliadin-induced toxicity in the intestinal epithelium. Endoscopy. 2009;136:288–298.
   Google Scholar
• Pinier M, Fuhrmann G, Galipeau HJ, et al. The copolymer P(HEMA-co-SS) binds gluten and reduces immune response in gluten-sensitized mice and human tissues. Endoscopy. 2012;142:316–25.e12.
   Google Scholar
• McCarville JL, Nisemblat Y, Galipeau HJ, et al. BL-7010 demonstrates specific binding to gliadin and reduces gluten-associated pathology in a chronic mouse model of gliadin sensitivity. D’Auria S, ed. PLoS ONE. 2014;9:e109972. DOI:10.1371/journal.pone.0109972
   PubMed Web of Science ®Google Scholar
• de Sousa Moraes LF, de Sousa Moraes LF, Grzeskowiak LM, et al. Intestinal microbiota and probiotics in celiac disease. Clin Microbiol Rev. 2014;27:482–489.
   PubMed Web of Science ®Google Scholar
• Smecuol E, Hwang HJ, Sugai E, et al. Exploratory, randomized, double-blind, placebo-controlled study on the effects of bifidobacterium infantis natren life start strain super strain in active celiac disease. J Clin Gastroenterol. 2013;47:139–147.
   PubMed Web of Science ®Google Scholar
• Angelis MD, Rizzello CG, Fasano A, et al. VSL#3 probiotic preparation has the capacity to hydrolyze gliadin polypeptides responsible for Celiac Sprue probiotics and gluten intolerance. Biochim Biophys Acta (BBA) Mol Basis Disease. 2006;1762:80–93.
   PubMed Web of Science ®Google Scholar
• Kelly CP, Green PH, Murray JA, et al. Larazotide acetate celiac disease study group larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. 2013;37:252–262.
   PubMed Web of Science ®Google Scholar
• Leffler DA, Kelly CP, Abdallah HZ, et al. A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. 2012 July. DOI:10.1038/ajg.2012.211.
   Web of Science ®Google Scholar
• Leffler DA, Kelly CP, Green PHR, et al. Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Endoscopy. 2015;148:1311–1319.e1316.
   Google Scholar
• Lebreton C, Ménard S, Abed J, et al. Interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides. Endoscopy. 2012;143:698–707.e4.
   Google Scholar
• Matysiak-Budnik T, Moura IC, Arcos-Fajardo M, et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med. 2008;205:143–154.
   PubMed Web of Science ®Google Scholar
• Induction May Prevent Celiac Enteritis. Available from: https://clinicaltrials.gov/ct2/show/NCT02929316
   Google Scholar
• Olaussen RW, Karlsson MR, Lundin KEA, et al. Reduced chemokine receptor 9 on intraepithelial lymphocytes in celiac disease suggests persistent epithelial activation. Endoscopy. 2007;132:2371–2382.
   Google Scholar
• Plugis NM, Khosla C. Therapeutic approaches for celiac disease. Best Pract Res Clin Gastroenterol. 2015;29:503–521.
   PubMed Web of Science ®Google Scholar
• Hamilton G, Mäki M, Lähdeaho M-L, et al. T1143: a randomized, double-blind, placebo-controlled, phase II study testing CCX282-B in the treatment of celiac disease. Endoscopy. 2008;134:A–493.
   Google Scholar
• Bach J-F. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347:911–920.
   PubMed Web of Science ®Google Scholar
• Altmann DM. Review series on helminths, immune modulation and the hygiene hypothesis: nematode coevolution with adaptive immunity, regulatory networks and the growth of inflammatory diseases. Immunology. 2009;126:1–2.
   PubMed Web of Science ®Google Scholar
• Aoyama H, Hirata T, Sakugawa H, et al. An inverse relationship between autoimmune liver diseases and Strongyloides stercoralis infection. Am J Trop Med Hyg. 2007;76:972–976. Available from: http://www.ajtmh.org/content/76/5/972.full
   PubMed Web of Science ®Google Scholar
• Moreels TG, Nieuwendijk RJ, de Man JG, et al. Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats. Gut. 2004;53:99–107.
   PubMed Web of Science ®Google Scholar
• Elliott DE, Li J, Blum A, et al. Exposure to schistosome eggs protects mice from TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol. 2003;284:G385–G391.
   PubMed Web of Science ®Google Scholar
• Daveson AJ, Jones DM, Gaze S, et al. Effect of hookworm infection on wheat challenge in celiac disease – a randomised double-blinded placebo controlled trial. Gluud LL, ed. PLoS ONE. 2011;6:e17366. DOI:10.1371/journal.pone.0017366
   PubMed Web of Science ®Google Scholar
• McSorley HJ, Gaze S, Daveson J, et al. Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection. Sestak K, ed. PLoS ONE. 2011;6:e24092. DOI:10.1371/journal.pone.0024092
   PubMed Web of Science ®Google Scholar
• Croese J, Giacomin P, Navarro S, et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J Allergy Clin Immunol. 2014 August. DOI:10.1016/j.jaci.2014.07.022.
   PubMed Web of Science ®Google Scholar
• Malamut G, Machhour El R. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease–associated inflammation and lymphomagenesis. J Clin Invest. 2010;120:2131–2143.
   PubMed Web of Science ®Google Scholar
• Di Sabatino A, Ciccocioppo R, Cupelli F, et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut. 2006;55:469–477.
   PubMed Web of Science ®Google Scholar
• Maiuri L, Ciacci C, Auricchio S, et al. Interleukin 15 mediates epithelial changes in celiac disease. Endoscopy. 2000;119:996–1006.
   Google Scholar
• Hüe S, Mention -J-J, Monteiro RC, et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity. 2004;21:367–377.
   PubMed Web of Science ®Google Scholar
• Yokoyama S, Yokoyama S, Watanabe N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci USA. 2009;106:15849–15854.
   PubMed Web of Science ®Google Scholar
• Yokoyama S, Perera P-Y, Waldmann TA, et al. Tofacitinib, a Janus Kinase inhibitor demonstrates efficacy in an IL-15 transgenic mouse model that recapitulates pathologic manifestations of celiac disease. J Clin Immunol. 2012;33:586–594.
   PubMed Web of Science ®Google Scholar
• Rauhavirta T, Oittinen M, Kivistö R, et al. Are transglutaminase 2 inhibitors able to reduce gliadin-induced toxicity related to celiac disease? A proof-of-concept study. J Clin Immunol. 2012;33:134–142.
   PubMed Web of Science ®Google Scholar
• Szondy Z, Szondy Z, Sarang Z, et al. Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. Proc Natl Acad Sci USA. 2003;100(13):7812–7817.
   PubMed Web of Science ®Google Scholar
• Huan J, Meza-Romero R, Mooney JL, et al. Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4+ T-cell proliferation and attenuate production of inflammatory cytokines: a potential therapy for celiac disease. Mucosal Immunol. 2010;4:112–120.
   PubMed Web of Science ®Google Scholar
• Jüse U, van de Wal Y, Koning F, et al. Design of new high-affinity peptide ligands for human leukocyte antigen-DQ2 using a positional scanning peptide library. Hum Immunol. 2010;71:475–481.
   PubMed Web of Science ®Google Scholar
• Tye-Din JA, Stewart JA, Dromey JA, et al. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med. 2010;2:41–51.
   Web of Science ®Google Scholar
• Keech CL, Dromey J, Chen Z, et al. 355 immune tolerance induced by peptide immunotherapy in an HLA Dq2-dependent mouse model of gluten immunity. Endoscopy. 2009;136(5):A–57.
   Google Scholar
• Aziz I, Evans KE, Papageorgiou V, et al. Are patients with coeliac disease seeking alternative therapies to a gluten-free diet? J Gastrointestin Liver Dis. 2011;20:27–31.
   PubMed Web of Science ®Google Scholar
• Assessment of Immune Activation and Tolerance in Celiac Disease. Available from: https://clinicaltrials.gov/ct2/show/NCT03409796?term=TIMP&cond=celiac&rank=1.
   Google Scholar
• Woodward J. The management of refractory coeliac disease. Ther Adv Chronic Dis. 2013;4:77–90. DOI:10.1177/2040622312473174.
   PubMedGoogle Scholar
• Brunner M, Ziegler S, Di Stefano AFD, et al. Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation. Br J Clin Pharmacol. 2006;61:31–38.
   PubMed Web of Science ®Google Scholar
• Edsbäcker S, Larsson P, Wollmer P. Gut delivery of budesonide, a locally active corticosteroid, from plain and controlled-release capsules. Eur J Gastroenterol Hepatol. 2002;14:1357.
   PubMed Web of Science ®Google Scholar
• Ciacci C, Maiuri L, Russo I, et al. Efficacy of budesonide therapy in the early phase of treatment of adult coeliac disease patients with malabsorption: an in vivo/in vitro pilot study. Clin Exp Pharmacol Physiol. 2009;36:1170–1176.
   PubMed Web of Science ®Google Scholar
• Brar P, Lee S, Lewis S, et al. Budesonide in the treatment of refractory celiac disease. Am J Gastroenterol. 2007;102:2265–2269.
   PubMed Web of Science ®Google Scholar
• Daum S, Ipczynski R, Heine B, et al. Therapy with budesonide in patients with refractory sprue. Digestion. 2006;73:60–68.
   PubMed Web of Science ®Google Scholar
• Oliva S, Rossetti D, Papoff P, et al. A new formulation of oral viscous budesonide in treating paediatric eosinophilic oesophagitis. J Pediatr Gastroenterol Nutr. 2017;64:218–224.
   PubMed Web of Science ®Google Scholar
• Miehlke S, Hruz P, Vieth M, et al. A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. Gut. 2016;65:390–399.
   PubMed Web of Science ®Google Scholar
• Newnham ED, Shepherd SJ, Gibson PR. A phase II, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of oral effervescent budesonide in the induction of mucosal healing in newly diagnosed coeliac disease: Australia and New Zealand Clinical Trials Registry: ACTRN12609000738224. Available from: anzctr.org.au. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=308403Accessed 18th February 2018.
   Google Scholar
• Goerres MS, Meijer JWR, Wahab PJ, et al. Azathioprine and prednisone combination therapy in refractory coeliac disease. Aliment Pharmacol Ther. 2003;18:487–494.
   PubMed Web of Science ®Google Scholar
• Turner SM, Moorghen M, Probert CSJ. Refractory coeliac disease: remission with infliximab and immunomodulators. Eur J Gastroenterol Hepatol. 2005;17:667–669.
   PubMed Web of Science ®Google Scholar
• Costantino G, Torre Della A, Presti Lo MA, et al. Treatment of life-threatening type I refractory coeliac disease with long-term infliximab. Digestive and Liver Disease. 2008;40:74–77.
   Web of Science ®Google Scholar
• Al-Toma A, Visser OJ, Van Roessel HM, et al. Autologous hematopoietic stem cell transplantation in refractory celiac disease with aberrant T cells. Blood. 2007;109:2243–2249.
   PubMed Web of Science ®Google Scholar
• Tack GJ, Wondergem MJ, Al-Toma A, et al. Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy. Bone Marrow Trans. 2010;46:840–846.
   PubMed Web of Science ®Google Scholar
• Rashtak S, Murray JA. Review article: coeliac disease, new approaches to therapy. Aliment Pharmacol Ther. 2012;35:768–781.
   PubMed Web of Science ®Google Scholar
• Caruso R, Marafini I, Sedda S, et al. Analysis of the cytokine profile in the duodenal mucosa of refractory coeliac disease patients. Clin Sci. 2014;126:451–458.
   PubMed Web of Science ®Google Scholar
• Rawal N, Twaddell W, Fasano A, et al. Remission of refractory celiac disease with infliximab in a pediatric patient. ACGCR. 2015;2:121–123.
   Google Scholar