Selective adhesion molecules of intestinal endothelial cells are therefore therapeutic targets for blocking leukocyte trafficking and activation in IBD, particularly because they do not induce systemic immune suppression. Natalizumab is a humanized monoclonal antibody directed against the cellular adhesion molecule α4-integrin. This agent blocks leukocyte adhesion to the endothelium in the intestinal tract, but also to the brain. The latter property led to its use in patients with multiple sclerosis. However, the development of progressive multifocal leukoencephalopathy (PML), a devastating and often fatal cerebral Abiraterone in vivo infection caused by the John Cunningham virus (JCV), has

limited it use in IBD. By targeting α4β7 integrin, the gut-specific mucosal addressin cell adhesion molecule (MAdCAM), PML may be prevented. Vedolizumab, a monoclonal antibody that blocks this interaction, and rhuMAb7, a monoclonal antibody against the β7 subunit are currently under investigation for IBD.4,5 (Fig. 1) This review article critically examines the indications of biological agents in the treatment of IBD, the practical issues on prescribing these drugs and their potential for adverse effects. In Australia, infliximab is approved

for use in refractory luminal and fistulizing CD and UC and adalimumab for refractory CD.6 Certolizumab has been evaluated in a phase 3 trial, and is approved for use in the USA and parts of Europe, but is not yet readily available in the Asia-Pacific region. All three agents have similar efficacy in comparable trials MLN8237 solubility dmso versus placebo. There are, as yet, no head-to-head trials. The newer agents have less long term follow up data. In Asia, anti-TNF treatment has been used for years in CD, with most data originating from Japan. The above three agents have demonstrated efficacy for patients with luminal CD but only infliximab so far has had primary endpoint data for fistulizing CD.7–10 Infliximab induces and maintains remission in UC4 and has been used as a salvage therapy for acute severe colitis in open labeled studies.11 The extra-intestinal manifestations of IBD may also benefit

from treatment with anti-TNF agents. Bone mineral density and osteoporosis may improve when patients are treated with anti-TNF 上海皓元医药股份有限公司 agents.12–14 Similarly, beneficial effects on colitic arthropathy and other extraintestinal manifestations have been noted.15–17 Refractory luminal Crohn’s disease.  The success of anti-TNF therapy in refractory luminal disease has been well demonstrated. Initial studies demonstrated the efficacy of induction therapy, but it is now known that maintenance therapy delivers superior long term outcomes.18,19 The ACCENT 1 study demonstrated the superiority of three dose infliximab induction over a single dose induction regimen.7 This study also demonstrated superiority of scheduled two-monthly maintenance therapy over episodic treatment.