Published online Feb 7, 2014. doi: 10.3748/wjg.v20.i5.1139
Revised: November 8, 2013
Accepted: January 6, 2014
Published online: February 7, 2014
Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.
Core tip: In this paper we critically review recently published literature about these novel therapies, which have been the results of extensive research identifying molecular targets. Several agents have been tested and show promising data, but we focus on vedolizumab, a monoclonal antibody against the α4β7 integrin on lymphocytes, ustekinumab, a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23, and tofacitinib, an orally administered small molecule targeting Janus-activated kinase. These three agents are most likely to find their way soon to the market and offer significant therapeutic advantages for the management of Crohn’s disease and ulcerative colitis.