Anti-TNF therapy in Crohn's disease

Abstract

Anti-tumour necrosis factor (TNF) strategies, the most studied of biological therapies, include chimeric monoclonal (infliximab), humanized monoclonal (CDP571 and the PEGylated CDP870) and fully human monoclonal (adalimumab) antibodies, p75 fusion protein (etanercept), p55 soluble receptor (onercept) and small molecules such as MAPkinase inhibitors. The principal use of infliximab is in treating active Crohn's disease patients not responding to or intolerant of conventional therapies. Infliximab is steroid sparing. The development of antibodies against infliximab is associated with an increased risk of infusion reactions, and a reduced duration of response to treatment, and concomitant immunosuppressive therapy reduces the immunogenic response. The demonstration of the efficacy of maintenance therapy every 8 weeks with infliximab in the randomised, controlled, ACCENT I trial opened up the strategy for regular maintenance. In patients who have failed therapy with cortocosteroids and immunosuppressive therapy and are poor surgical candidates, and patients with fistulizing disease, where infliximab therapy is chosen, regular maintenance therapy with infliximab is likely to be required. On the other hand, patients with severely active, steroid-refractory disease in whom immunosuppressive therapy and infliximab are initiated together, may respond adequately and be continued on long-term immunosuppressive therapy alone. In ulcerative colitis the role of infliximab remains uncertain.