Optimising Biologic Therapies for Maximal Effect in Crohn s Disease

Optimising Biologic Therapies for Maximal Effect in Crohn s Disease

Remo Panaccione
European Gastroenterology Review 2007 - December 2007
Published: October 2008
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Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the intestinal tract for which there is no medical cure. Thus, the aim of current treatment is to induce and maintain remission while achieving the highest quality of life for the patient. The introduction of biologics, in particular of anti-tumour necrosis factor (TNF)-alpha, has significantly advanced IBD therapy and greatly expanded the range of options available to patients and physicians. Infliximab, a murine chimaeric monoclonal antibody directed against TNF-alpha, was first approved by the US Food and Drug Administration (FDA) in 1998 for the treatment of adult patients with Crohn’s disease (CD). This was followed shortly thereafter by European approval in 1999 for induction of remission for severe active luminal CD and fistulising CD. Since then, infliximab has been approved for maintenance of remission in severe active CD as well as in fistulising CD. Furthermore, infliximab is approved for induction and maintenance of severe active paediatric CD and moderate to severe ulcerative colitis (UC).

Overview of Pivotal Anti-tumour Necrosis Factor Trials
Infliximab was the first and has been the most extensive anti-TNF agent evaluated in the treatment of IBD. It has been shown to be effective for the induction and maintenance of clinical remission in moderate to severe luminal CD1–3 and the induction and maintenance of remission in fistulising CD.4,5 Furthermore, it has been shown to be associated with endoscopic healing, decreased rates of hospitalisation and surgery and improved quality of life in patients with CD.6–8 It is the only anti-TNF agent approved for moderate to severe outpatient UC and has been shown to improve colectomy-free survival in patients with severe hospitalised UC.9–11

Adalimumab, a monoclonal antibody of human origin, has been shown to be effective for the induction and maintenance of remission of moderate to severe CD.12–14 It can also be used in patients who have lost response to, or have become intolerant of, infliximab.13 Data from the CHARM study showed that patients on adalimumab maintenance therapy have an 8.4% absolute risk reduction and a 57% relative risk reduction of hospitalisation compared with those on placebo.15 The ability of adalimumab to achieve mucosal healing in CD, its exact benefit in fistulising CD and its efficacy in patients with UC remain unknown.

In clinical trials, the humanised pegylated FAb fragment certolizumab has been shown to be effective for the induction and maintenance of remission in patients with moderate to severe CD.16,17 Certolizumab has recently received regulatory approval for CD in Switzerland. The ability of certolizumab to achieve mucosal healing and reduce the rate of hospitalisation and surgery remains unknown. Furthermore, no data are available for its efficacy in fistulising CD.

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