Περίληψη:
After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effective alternative. With 2 currently approved drugs (ie, natalizumab, vedolizumab) and several others in phase 3 trials (eg, etrolizumab, ozanimod, anti-MAdCAM-1), the blockade of trafficking molecules has firmly emerged as a new therapeutic era for IBD. We discuss the targets that have been explored in clinical trials: chemokines and its receptors (eg, IP10, CCR9), integrins (eg, natalizumab, AJM300, vedolizumab, and etrolizumab), and its endothelial ligands (MAdCAM-1, ICAM-1). We also discuss a distinct strategy that interferes with lymphocyte recirculation by blocking lymphocyte egress from lymph nodes (small molecule sphingosine-phosphate receptor [S1PR] agonists: fingolimod, ozanimod, etrasimod, amiselimod). Strategies on the horizon include additional small molecules, allosteric inhibitors that specifically bind to the active integrin form and nanovectors that allow for the use of RNA interference in the quest to modulate pro-inflammatory leukocyte trafficking in IBD. © 2018 Crohn's & Colitis Foundation. Published by Oxford University Press. All rights reserved.
Συγγραφείς:
Pérez-Jeldres, T.
Tyler, C.J.
Boyer, J.D.
Karuppuchamy, T.
Bamias, G.
Dulai, P.S.
Boland, B.S.
Sandborn, W.J.
Patel, D.R.
Rivera-Nieves, J.
Λέξεις-κλειδιά:
abrilumab; agents used in inflammatory bowel disease; ajm 300; amiselimod; chemokine; chemokine receptor; efalizumab; et 3764; etrasimod; etrolizumab; fingolimod; gsk 3050002; integrin; intercellular adhesion molecule 1; mocravimod; morphotek; natalizumab; ozanimod; pf 00547659; pravastatin; ptg 100; shp 647; sphingosine 1 phosphate receptor; unclassified drug; vedolizumab; gastrointestinal agent, cell cycle arrest; cell migration; clinical effectiveness; clinical feature; drug effect; drug efficacy; drug response; human; inflammatory bowel disease; intervention study; pathogenesis; priority journal; protein targeting; Review; RNA interference; signal transduction; treatment outcome; animal; cell motion; drug effect; inflammatory bowel disease; leukocyte; pathology, Animals; Cell Movement; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Leukocytes
