When combination therapy isn't working: emerging therapies for the management of inflammatory bowel disease

World J Gastroenterol. 2014 Feb 7;20(5):1139-46. doi: 10.3748/wjg.v20.i5.1139.

Abstract

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.

Keywords: Emerging therapies; Inflammatory bowel disease; Tofacitinib; Ustekinumab; Vedolizumab.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / therapeutic use*
  • Drug Design
  • Drug Substitution
  • Drug Therapy, Combination
  • Gastrointestinal Agents / chemistry
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Intestines / immunology
  • Molecular Targeted Therapy
  • Signal Transduction / drug effects
  • Treatment Failure

Substances

  • Anti-Inflammatory Agents
  • Gastrointestinal Agents