Topical treatment with the toll-like receptor agonist DIMS0150 has potential for lasting relief of symptoms in patients with chronic active ulcerative colitis by restoring glucocorticoid sensitivity

Inflammatory Bowel Diseases

Volumn 19, Issue 2, 2013, Pages 283-292

  Musch, Eugen ^a   Lutfi, Tamim ^a   Von Stein, Petra ^b   Zargari, Arezou ^b   Admyre, Charlotte ^c   Malek, Mouhamad ^a   Löfberg, Robert ^c   Von Stein, Oliver D ^b  

^a Marien Hospital Bottrop gGmbH   (Germany)

^b InDex Pharmaceutical AB   (Sweden)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Colectomy; Dims0150; Steroid resistance; Toll like receptor agonist; Ulcerative colitis

Indexed keywords

AZATHIOPRINE; DIMS 0150; IMMUNOMODULATING AGENT; INFLIXIMAB; INTERLEUKIN 6; PREDNISOLONE; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ADD ON THERAPY; ADOLESCENT; ADULT; ARTICLE; CHILD; CLINICAL ARTICLE; CLINICAL ASSESSMENT; CLINICAL EVALUATION; COLON RESECTION; COLONOSCOPE; DISEASE ACTIVITY; DRUG EFFICACY; DRUG MEGADOSE; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; HISTOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; INFANT; MALE; OUTPATIENT; PHASE 3 CLINICAL TRIAL; PRESCHOOL CHILD; PRIORITY JOURNAL; REMISSION; SCHOOL CHILD; SINGLE DRUG DOSE; SYMPTOM; TREATMENT RESPONSE; ULCERATIVE COLITIS;

ADMINISTRATION, TOPICAL; ADULT; AGED; BIOLOGICAL MARKERS; COLITIS, ULCERATIVE; COLON; COLONOSCOPY; DNA; DRUG ADMINISTRATION SCHEDULE; DRUG THERAPY, COMBINATION; FEMALE; FOLLOW-UP STUDIES; GLUCOCORTICOIDS; HUMANS; IMMUNOLOGIC FACTORS; INTERLEUKIN-6; MALE; MIDDLE AGED; PREDNISOLONE; PROSPECTIVE STUDIES; TOLL-LIKE RECEPTOR 9; TREATMENT OUTCOME;

EID: 84876412015     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1002/ibd.23019     Document Type: Article

References (41)

1. Lees CW. Genetics of ulcerative colitis. Inflamm Bowel Dis. 2011: 831-848.
2. Cho JH, Brant SR. Recent insights into the genetics of inflammatory bowel disease. Gastroenterology. 2011;140:1704-1712.
3. Wine E, Ossa JC, Gray-Owen SD, et al. Adherent-invasive Escherichia coli target the epithelial barrier. Gut Microbes. 2010;1:80-84.
4. Cosnes J. Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD. Dig Dis. 2010;28:411-417.
5. Schmitz H, Barmeyer C, Fromm M, et al. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999;116:301-309.
6. Heller F, Fuss IJ, Nieuwenhuis EE, et al. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NKT cells. Immunity. 2002;17:629-638.
7. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427-434.
8. Riegler G, Tartaglione MT, Carratú R, et al. Age-related clinical severity at diagnosis in 1705 patients with ulcerative colitis. Dig Dis Sci. 2000;45: 462-465.
9. Faubion WA Jr, Loftus EV Jr, Harmsen WS, et al. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121:255-260.
10. Turner D, Walsh CM, Steinhart AH, et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a metaregression. Clin Gastroenterol Hepatol. 2007;5:103-110.
11. Wilhelm SM, McKenney KA, Rivait KN, et al. A review of infliximab use in ulcerative colitis. Clin Ther. 2008;30:223-230.
12. Filippi J, Allen PB, Hébuterne X, et al. Does anti-TNF therapy reduce the requirement for surgery in ulcerative colitis? A systematic review. Curr Drug Targets. 2011;12:1440-1447.
13. SjöbergM, Walch A, MeshkatM, et al. Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis: a retrospective observational study. Inflamm Bowel Dis. 2012;18:212-218.
14. Langholz E, Munkholm P, Davidsen M, et al. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107:3-11.
15. Triantafillidis JK, Merikas E, Georgopoulos F. Current and emerging drugs for the treatment of inflammatory bowel disease. Drug Des Devel Ther. 2011;5:185-210.
16. Kamm MA, Lichtenstein GR, Sandborn WJ, et al. Effect of extended MMX mesalamine therapy for acute, mild-to-moderate ulcerative colitis. Inflamm Bowel Dis. 2009;15:1-8.
17. Abreu MT. Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol. 2010; 10:131-144.
18. Maldonado-Contreras AL, McCormick BA. Intestinal epithelial cells and their role in innate mucosal immunity. Cell Tissue Res. 2011;343:5-12.
19. Lemaitre B, Nicolas E, Michaut L, et al. The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86:973-983.
20. Poltorak A, He X, Smirnova I, Liu MY, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998;282:2085-2088.
21. Creed TJ, Lee RW, Newcomb PV, et al. The effects of cytokines on suppression of lymphocyte proliferation by dexamethasone. J Immunol. 2009;183:164-171.
22. Franchimont D, Martens H, Hagelstein MT, el al. Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor. J Clin Endocrinol Metab. 1999;84:2834-2839.
23. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298:82-86.
24. Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis (comment). Gut. 2000;47:404-409.
25. Duclos M, Gouarne C, Bonnemaison D. Acute and chronic effects of exercise on tissue sensitivity to glucocorticoids. J Appl Physiol. 2003; 94:869-875.
26. DeRijk RH, Petrides J, Deuster P, et al. Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans. J Clin Endocrinol Metab. 1996;81:228-235.
27. Hearing SD, Norman M, Probert CSJ, et al. Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes. Gut. 1999:45:382-388.
28. Fazio VW, Ziv Y, Church JM, et al. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg. 1995;222:120-127.
29. Weinryb RM, Gustavsson JP, Liljeqvist L, et al. A prospective study of the quality of life after pelvic pouch operation. J Am Coll Surg. 1995;180: 589-595.
30. Ferrante M, Declerck S, De Hertogh G, et al. Outcome after proctocolectomy with ileal poucheanal anastomosis for ulcerative colitis. Inflamm Bowel Dis. 2008;14:20-28.
31. Rubin DT, Siegel CA, Kane SV, et al. Impact of ulcerative colitis from patients' and physicians' perspectives: results from the UC: normal survey. Inflamm Bowel Dis. 2009;15:581-588.
32. Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009;137:1250-1260.
33. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194-1201.
34. Niv Y, Bat L, Ron E, et al. Change in the extent of colonic involvement in ulcerative colitis: a colonoscopic study. Am J Gastroenterol. 1987;82: 1046-1051.
35. Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451.
36. Hanauer SB, Sandborn W. Management of Crohn's disease in adults. Am J Gastroenterol. 2001;96:635-643.
37. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet. 2007;369: 1641-1657.
38. Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994;330: 1841-1845.
39. Sharkey L, Bredin F, Nightingale A, et al The use of cyclosporin A in acute steroid-refractory ulcerative colitis: long term outcomes. J Crohns Colitis. 2011;5:91-94.
40. Ellis MC, Diggs BS, Vetto JT, et al. Trends in the surgical treatment of ulcerative colitis over time: increased mortality and centralization of care. World J Surg. 2011;35:671-676.
41. Roberts SE, Williams JG, Yeates D, et al. Mortality in patients with and without colectomy admitted to hospital for ulcerative colitis and Crohn's disease: record linkage studies. BMJ. 2007;335:1033.