Emerging biological treatments in inflammatory bowel diseases

Although the advent of infliximab has changed the treatment paradigm and goals in inflammatory bowel diseases (IBD), it does not provide a cure for IBD and recent evidence has demonstrated that the immunogenicity of this chimeric anti tumor necrosis factor (TNF) antibody is associated with secondary loss of response and intolerance. In ulcerative colitis the efficacy of infliximab was demonstrated in two large clinical trials, but long term maintenance efficacy data are lacking. Novel biological agents have entered clinical development and pioneering trials have been reported in the last two years. For Crohn's disease the fully human IgG1 anti TNF monoclonal adalimumab, the humanized pegylated Fab-fragment certolizumab-pegol and the humanized anti a4 integrin IgG4 antibody, natalizumab have yielded the most promising results in controlled trials, but also agents inhibiting the crucial IL12/interferon-g feedback loop suggest therapeutic potential. For severe ulcerative colitis infliximab has been shown to be an effective rescue treatment and the anti T-cell CD3 antibody has shown promising open label

Crucial in the development of novel biological agents, however, is the benefit risk ratio. As illustrated by unexpected but devastating brain infections with antiadhesion molecules, clinicians should be aware that the powerful immunomodulatory capacity of biologicals necessitates a rigorous safety follow-up.