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http://dx.doi.org/10.3904/kjm.2013.85.6.578

Natural Course of Crohn's Disease and Novel Treatment Drugs  

Lee, Jin Ha (Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine)
Cheon, Jae Hee (Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine)
Publication Information
The Korean Journal of Medicine / v.85, no.6, 2013 , pp. 578-585 More about this Journal
Abstract
Crohn's disease is a chronic recurrent inflammatory disease, mainly affecting the gastrointestinal tract. The pathogenesis of inflammatory bowel disease is believed to be caused by the complex interplay of many factors including host genetic susceptibility, the external environment such as infectious agents or the commensal enteric flora, and the immune system dysfunction. Advances in the understanding of the pathophysiology of inflammatory bowel disease have resulted in the development of multiple biological agents that all represent an alternative to the use of current therapies in patients with refractory Crohn's disease. Moreover, these biologic agents are expected to change the natural course of inflammatory bowel disease. Among them, anti-tumor necrosis factor (TNF)-${\alpha}$ agent is the first developed drug, and it dramatically improved the IBD management. However, more than one-third of the patients do not respond to the drugs due to antibody formation and loss of response. To increase treatment efficacy, enormous efforts have been made to develop novel anti-cytokines which can be an alternative to anti-TNF-${\alpha}$ agents. They are anti-CD4+ T cell cytokines including interleukin (IL)-12/23, IL-17A, and IFN-${\gamma}$ blockers, selective anti-adhesion molecules, anti-inflammatory cytokine IL-10, and immune stimulators. This paper reviews the natural history of Crohn's disease, natural course modifiers, and the efficacy and safety of biologic agents other than anti-TNF ${\alpha}$ agents.
Keywords
Crohn's disease; Inflammatory bowel disease; Natural history; Biologic agent; Anti-TNF agent;
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1 Ford AC, Sandborn WJ, Khan KJ, Hanauer SB, Talley NJ, Moayyedi P. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011;106:644-659.   DOI   ScienceOn
2 Langer-Gould A, Atlas SW, Green AJ, Bollen AW, Pelletier D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005;353:375-381.   DOI   ScienceOn
3 Feagan BG, Greenberg GR, Wild G, et al. Treatment of active Crohn's disease with MLN0002, a humanized antibody to the alpha4beta7 integrin. Clin Gastroenterol Hepatol 2008;6: 1370-1377.   DOI   ScienceOn
4 Yacyshyn BR, Bowen-Yacyshyn MB, Jewell L, et al. A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. Gastroenterology 1998;114: 1133-1142.   DOI   ScienceOn
5 Schreiber S, Nikolaus S, Malchow H, et al. Absence of efficacy of subcutaneous antisense ICAM-1 treatment of chronic active Crohn's disease. Gastroenterology 2001;120:1339-1346.   DOI   ScienceOn
6 Yacyshyn BR, Chey WY, Goff J, et al. Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease. Gut 2002;51:30-36.   DOI   ScienceOn
7 Braat H, Rottiers P, Hommes DW, et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol 2006;4:754-759.   DOI   ScienceOn
8 Sands BE, Bank S, Sninsky CA, et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease. Gastroenterology 1999; 117:58-64.   DOI   ScienceOn
9 Sands BE, Winston BD, Salzberg B, et al. Randomized, controlled trial of recombinant human interleukin-11 in patients with active Crohn's disease. Aliment Pharmacol Ther 2002; 16:399-406.   DOI   ScienceOn
10 Herrlinger KR, Witthoeft T, Raedler A, et al. Randomized, double blind controlled trial of subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn's disease. Am J Gastroenterol 2006;101:793-797.   DOI   ScienceOn
11 Pena Rossi C, Hanauer SB, Tomasevic R, Hunter JO, Shafran I, Graffner H. Interferon beta-1a for the maintenance of remission in patients with Crohn's disease: results of a phase II dose-finding study. BMC Gastroenterol 2009;9:22.   DOI   ScienceOn
12 Kim KO, Jang BI. Emerging drugs in the treatment of inflammatory bowel disease: beyond anti-TNF-$\alpha$. Korean J Gastroenterol 2011;58:235-244.   DOI   ScienceOn
13 Marks DJ, Harbord MW, MacAllister R, et al. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet 2006;367:668-678.   DOI   ScienceOn
14 Smith AM, Rahman FZ, Hayee B, et al. Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. J Exp Med 2009;206:1883-1897.   DOI   ScienceOn
15 Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001;411:603-606.   DOI   ScienceOn
16 Dejaco C, Lichtenberger C, Miehsler W, et al. An open-label pilot study of granulocyte colony-stimulating factor for the treatment of severe endoscopic postoperative recurrence in Crohn's disease. Digestion 2003;68:63-70.   DOI   ScienceOn
17 Dieckgraefe BK, Korzenik JR. Treatment of active Crohn's disease with recombinant human granulocyte-macrophage colony-stimulating factor. Lancet 2002;360:1478-1480.   DOI   ScienceOn
18 Reinisch W, Hommes DW, Van Assche G, et al. A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease. Gut 2006;55:1138-1144.
19 Hommes DW, Mikhajlova TL, Stoinov S, et al. Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut 2006;55:1131-1137.
20 Reinisch W, de Villiers W, Bene L, et al. Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm Bowel Dis 2010;16:233-242.   DOI   ScienceOn
21 Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION Study. Ann Rheum Dis 2010;69:88-96.   DOI   ScienceOn
22 Nishimoto N, Ito K, Takagi N. Safety and efficacy profiles of tocilizumab monotherapy in Japanese patients with rheumatoid arthritis: meta-analysis of six initial trials and five long-term extensions. Mod Rheumatol 2010;20:222-232.   DOI
23 Berg DJ, Davidson N, Kühn R, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 1996;98:1010-1020.   DOI   ScienceOn
24 Van Deventer SJ, Elson CO, Fedorak RN. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease: Crohn's Disease Study Group. Gastroenterology 1997; 113:383-389.   DOI   ScienceOn
25 Fedorak RN, Gangl A, Elson CO, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease: the Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 2000;119:1473-1482.   DOI   ScienceOn
26 Schreiber S, Fedorak RN, Nielsen OH, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease: Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology 2000;119:1461-1472.   DOI   ScienceOn
27 Colombel JF, Rutgeerts P, Malchow H, et al. Interleukin 10 (Tenovil) in the prevention of postoperative recurrence of Crohn's disease. Gut 2001;49:42-46.   DOI   ScienceOn
28 Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359:1541-1549.   DOI   ScienceOn
29 Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004;350:876-885.   DOI   ScienceOn
30 Regueiro M, Schraut W, Baidoo L, et al. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology 2009;136:441-450.e1.   DOI   ScienceOn
31 D'haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European Multicenter Trial. Gastroenterology 1999;116:1029-1034.   DOI   ScienceOn
32 Feagan BG, Panaccione R, Sandborn WJ, et al. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM Study. Gastroenterology 2008;135:1493-1499.   DOI   ScienceOn
33 Danese S. New therapies for inflammatory bowel disease: from the bench to the bedside. Gut 2012;61:918-932.   DOI   ScienceOn
34 Fuss IJ, Becker C, Yang Z, et al. Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. 2006;12:9-15.   DOI   ScienceOn
35 Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 2007;25:821-852.   DOI   ScienceOn
36 MacDonald TT, Monteleone I, Fantini MC, Monteleone G. Regulation of homeostasis and inflammation in the intestine. Gastroenterology 2011;140:1768-1775.   DOI   ScienceOn
37 Semerano L, Assier E, Delavallée L, Boissier MC. Kinoid of human tumor necrosis factor-alpha for rheumatoid arthritis. Expert Opin Biol Ther 2011;11:545-550.   DOI   ScienceOn
38 Sandborn WJ, Feagan BG, Fedorak RN, et al. A randomized trial of Ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. 2008;135:1130-1141.
39 Mannon PJ, Fuss IJ, Mayer L, et al. Anti-interleukin-12 antibody for active Crohn's disease. N Engl J Med 2004;351: 2069-2079.   DOI   ScienceOn
40 Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 2008;103:3167-3182.   DOI   ScienceOn
41 Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet 2007;369:1627-1640.   DOI   ScienceOn
42 Engel MA, Neurath MF. New pathophysiological insights and modern treatment of IBD. J Gastroenterol 2010;45:571-583.   DOI
43 Kornbluth A. Infliximab approved for use in Crohn's disease: a report on the FDA GI Advisory Committee conference. Inflamm Bowel Dis 1998;4:328-329.   DOI
44 Magro F, Portela F. Management of inflammatory bowel disease with infliximab and other anti-tumor necrosis factor alpha therapies. BioDrugs 2010;24(Suppl 1):3-14.   DOI   ScienceOn
45 Bouguen G, Peyrin-Biroulet L. Surgery for adult Crohn's disease: what is the actual risk? Gut 2011;60:1178-1181.   DOI   ScienceOn
46 Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J. Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001;49:777-782.   DOI   ScienceOn
47 Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn's disease. Inflamm Bowel Dis 2002; 8:244-250.   DOI   ScienceOn
48 Michelassi F, Balestracci T, Chappell R, Block GE. Primary and recurrent Crohn's disease: experience with 1379 patients. Ann Surg 1991;214:230-238.   DOI   ScienceOn
49 Greenstein AJ, Lachman P, Sachar DB, et al. Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms. Gut 1988;29:588-592.   DOI
50 Candy S, Wright J, Gerber M, Adams G, Gerig M, Goodman R. A controlled double blind study of azathioprine in the management of Crohn's disease. Gut 1995;37:674-678.   DOI   ScienceOn
51 Shanahan WR Jr. ISIS 2302, an antisense inhibitor of intercellular adhesion molecule 1. Expert opin Investig Drugs 1999;8:1417-1429.   DOI   ScienceOn
52 Korzenik JR, Dieckgraefe BK. An open-labelled study of granulocyte colony-stimulating factor in the treatment of active Crohn's disease. Aliment Pharmacol Ther 2005;21: 391-400.   DOI   ScienceOn
53 Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID Study. Inflamm Bowel Dis 2008;14:542-549.   DOI   ScienceOn
54 Peyrin-Biroulet L, Lemann M. Review article: remission rates achievable by current therapies for inflammatory bowel disease. Aliment Pharmacol Ther 2011;33:870-879.   DOI   ScienceOn
55 Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology 2000; 119:895-902.   DOI   ScienceOn
56 Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ. The natural history of adult Crohn's disease in populationbased cohorts. Am J Gastroenterol 2010;105:289-297.   DOI   ScienceOn
57 Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ; Sargramostim in Crohn's Disease Study Group. Sargramostim for active Crohn's disease. N Engl J Med 2005;352:2193-2201.   DOI   ScienceOn
58 Valentine JF, Fedorak RN, Feagan B, et al. Steroid-sparing properties of sargramostim in patients with corticosteroid- dependent Crohn's disease: a randomised, double-blind, placebo- controlled, phase 2 study. Gut 2009;58:1354-1362.   DOI   ScienceOn
59 Kelsen JR, Rosh J, Heyman M, et al. Phase I trial of sargramostim in pediatric Crohn's disease. Inflamm Bowel Dis 2010;16:1203-1208.   DOI   ScienceOn
60 Gordon FH, Lai CW, Hamilton MI, et al. A randomized placebo- controlled trial of a humanized monoclonal antibody to alpha4 integrin in active Crohn's disease. Gastroenterology 2001;121:268-274.   DOI   ScienceOn
61 Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Gastroenterology 2007;132:1672-1683.   DOI   ScienceOn
62 Ito H, Takazoe M, Fukuda Y, et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 2004;126:989-996.   DOI   ScienceOn