[Emerging Therapies: What Are Promising in the Near Future?]

Korean J Gastroenterol. 2018 Feb 25;71(2):81-88. doi: 10.4166/kjg.2018.71.2.81.
[Article in Korean]

Abstract

The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.

Keywords: Crohn's disease; Tofacitinib; Ulcerative colitis; Ustekinumab; Vedolizumab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Colitis, Ulcerative / drug therapy*
  • Crohn Disease / drug therapy*
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Tumor Necrosis Factor-alpha / immunology
  • Ustekinumab / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Gastrointestinal Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • tofacitinib
  • vedolizumab
  • Ustekinumab