European Gastroenterology & Hepatology Review, 2008;4(1):56-59
Due to the relapsing course of disease, patients with ulcerative colitis (UC) and Crohn’s disease (CD) often require extensive long-term treatment for the induction and maintenance of remission. Novel therapies are important since our current treatment modalities are not adequate for all patients. Although significant advances have been made in the treatment of patients with inflammatory bowel disease (IBD), there remains a substantial number of patients who have inadequate response, loss of response or adverse events with current therapies. With increased pathophysiological knowledge, new therapeutic strategies have been developed over the last few years that are available for these patients. Most of them belong to the group of biologic therapies and modulate the mucosal response by interacting with cytokines or activated immune cells. However, alternative treatment concepts and approaches should not be overlooked.
Biologic therapeutic strategies that have been tested or are still partly under investigation in multicentre studies include inhibitors of pro-inflammatory cytokines (e.g. anti-tumour necrosis factor [TNF] antibodies), inhibitors of lymphocyte polarisation and proliferation (e.g. antibodies against interleukin [IL]-12, IL-2, IL-10), inhibitors of leukocyte trafficking (e.g. antibodies against α4-integrin, chemokin-receptor antagonists or intercellular adhesion molecule [ICAM] antisense oligonucleotide), growth factors and hormones (e.g. keratinocyte growth factor), immunostimulating factors (e.g. granulocyte cell-stimulating factor [G-CSF] and granulocyte macrophage colony-stimulating factor [GM-CSF]) and immunomodulators (e.g. α-interferon [INF] and IL-11).
The most prominent biologic strategy is the anti-TNF approach using chimerised or humanised full or F(ab)-fragmented anti-TNF antibodies. An early multicentre, double-blind study on 108 patients with moderate to severe CD refractory to 5-ASA, corticosteroids and/or immunomodulators showed an 81% initial response rate at four weeks in patients receiving 5mg/kg infliximab compared with 17% in those receiving placebo.1 Additionally, the results of two large studies with the chimeric anti-TNF antibody infliximab in CD – A Crohn’s Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regime (ACCENT) I and II – were able to demonstrate long-term response in approximately 43–53% of patients; however, steroid-free remission could be achieved in only onethird of patients initially responding and treated over one year with the antibody, while 41% of patients did not improve after drug application.2 Patients with perianal fistula also responded to anti-TNF treatment for 14 weeks compared with placebo in terms of reduction of fistula secretion (49 versus 27%) and fistula closure (40 versus 23%).3 However, re-opening of fistulae after infliximab treatment was frequent, suggesting the persistence of deep fistulous tracts despite superficial healing. Overall, a European expert panel agreed that infliximab is appropriate for corticosteroid dependence, steroid refractoriness or steroid intolerance, and that anti-TNF antibody treatment can be considered after failure of either azathioprine/6-mercaptopurine or MTX in patients with CD.4
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