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Review

Recent developments in the pharmacological treatment of Crohn’s disease

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Pages 373-391 | Published online: 02 Mar 2005

Bibliography

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  • •A pilot study that has shown treatment benefit of onercept in CD.
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  • •Has shown that CD patients with elevated levels of CRP may be a different subgroup in terms of treatment response to anti-TNF therapy.
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  • •This study failed to show efficacy of rhIL-10 in treatment of mild-to-moderately active CD.
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  • ••This novel approach, by using adenoviralvectors to induce murine colonic IL-10 production and thereby restore mucosal immune homeostasis, is ground breaking and bodes well for future human studies.
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  • •Animal studies of this agent have shown that it can reduce colonic inflammation and TH1 cell activation. Human studies are awaited as CD is a predominantly TH1 disease and this drug should prove beneficial.
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  • ••CD patients showed both response andremission of their disease at week 6 when they received two infusions of the drug. Quality-of-life scales also showed an improvement.
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  • •This study tested the hypothesis that impaired neutrophil and/or monocyte function is the underlying pathogenic defect in some CD patients rather than excessive T-cell response by treating patients with GM-CSF versus placebo.
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  • •Raised the possibility that a PPAR-y heterodimer may be of therapeutic benefit in colonic inflammation.
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  • •The re-use of coherin, a peptide extract of bovine and porcine posterior pituitary gland that had been used several years ago, has stimulated interest in this agent as an alternative treatment for CD.
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  • •The first pilot study of the use of DHEA in CD based on the fact that some CD patients have decreased levels of DHEAS and that DHEA inhibits the activation of NF-x13.
  • CHIKANO S, SAWADA K, SHIMOYAMA T et al.: IL-18 and IL-12 induce inflammation and fatty liver in mice in an interferon gamma dependent manner. Gut (2000) 47:779–786.
  • SIEGMUND B, RIEDER F, ALBRICH S et al.: Adenosine kinase inhibitor GP515 improves experimental colitis in mice. Pharmacol Exp. Then (2001) 296(1):99–105.
  • RUTGEERTS P, REINISCH W, COLOMBEL JF et al.: Preliminary results of a Phase I/II study of Huzaf, an anti-interferon gamma monoclonal antibody, in patients with moderate to severe active Crohn's disease. Proceedings of the Digestive Disease Week, San Francisco, USA (2002):A505.
  • •A different approach to treatment of CD as IFN-y is thought to be a key cytokine that enhances the development of a TH1 irmrtune response and also suppresses the proliferation of TH2 cells.
  • DUBINSKY MC, HASSARD PV, SEIDMAN EG et al: An open label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy. Inflamm. Bowel Dis. (2001) 7:181–189.
  • DUBINSKY MC, FELDMAN EJ, ABREU MT, TARGAN SR, VASILIAUSKAS EA: Thioguanine (6-TG): a potential alternate thiopurine for IBD patients allergic to 6-mercaptopurine or azathioprine. Am. J. Gastroenterol (2003) 98:1058–1063.
  • HERRLINGER KR, KREISEL W, SCHWAB M et al.: Open prospective trial on 6-thioguanine for chronic active Crohn's disease. Proceedings of the Digestive Disease Week, San Francisco, CA, USA (2002):A432.
  • STORK LC, ERDMARU G, ADAMSON P et al.: Oral 6-thioguanine (TG) causes relatively mild and reversible hepatic veno-occlusive disease (VOD). Proceedings of the Annual Meeting of the Hematology Oncology (Huntingt) Society (1998):A672.
  • DUBINSKY MC, VASILIAUSKAS EA, SINGH H et al.: 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients. Gastroenterology (2003) 125:298–303.
  • •Raises awareness of NRH as a side effect of using 6-TG to treat IBD patients.
  • PRAJAPATI DN, KNOX JF, EMMONS J, SAEIAN K, CSUKA ME, BINION DG: Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy. J. Clio. Gastroenterol (2003) 37(2):125–128.
  • •Use of an irnmunomodulator not previously used to treat IBD helps with expanding the therapeutic armarnentariurn. oa. SANDBORN WJ, PRESENT DH, ISAACS KL et al.: Tacrolimus for the treatment of fistulas in patients with Crohn's disease: A randomized, placebo-controlled trial. Gastroenterology (2003) 125:380–388.
  • RUTGEERTS P, VAN ASSCHE G, D'HAENS G et al.: Ornidazole for prophylaxis of postoperative Crohn's disease: Final results of a double blind placebo controlled trial. Proceedings of the Digestive Disease Week, San Francisco, CA, USA. (2002):A80.
  • ••First report of a potentially useful agent toprevent or delay post-operative recurrence of CD, but patient noncompliance may be an issue secondary to drug side effects.
  • SHAFRAN I, JOHNSON LK, HAMM L, MURDOCK RH: Efficacy and tolerability of rifaximin, a non-absorbed oral antibiotic in the treatment of active Crohn's disease: Results of an open-label study. Proceedings of the American College of Gastroenterology Annual Meeting, Baltimore, USA (2003):A281.
  • •A non-absorbable oral antibiotic that appears to be of benefit in CD though a randomised, double-blind, placebo-controlled trial is awaited for confirmation of this benefit and lack of side effects.
  • STALLMACH A, WITTIG BM, MOSER C et al.: Safety and efficacy of intravenous pulse cyclophosphamide in acute steroid refractory inflammatory bowel disease. Gut (2003) 52:377–382.
  • •Preliminary data on a chemotherapeutic agent that may prove to be useful in CD patients.
  • Expert Op/n. Investig. Drugs (2004) 13(4)
  • REINISCH W, NAHAVANDI H, SANTELLA R et al.: Extracorporeal photochemotherapy in patients with steroid-dependent Crohn's disease: a prospective pilot study. Aliment. Pharmacol. Ther. (2001) 15:1313–1322.
  • DITSCHKOWSKI M, EINSELE H, SCHWERDTFEGER R et al: Improvement of inflammatory bowel disease after allogeneic stem-cell transplantation. Transplantation (2003) 75(10):1745–1747.
  • SUMMERS RW, ELLIOTT DE, QADIR K et al.: Triclomis suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am. Gastiventerol (2003) 98:2034–2041.
  • •Preliminary data on the use of non-disease-producing intestinal helminthes to induce a TH2 response and downregulate a chronic TH1 response, which is thought to be one of the pathogenesic mechanisms of CD.

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