Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases.

Abstract

Insights into the pathogenesis of inflammatory bowel diseases (IBDs) have provided important information for the development of therapeutics. Levels of interleukin 23 (IL23) and T-helper (Th) 17 cell pathway molecules are increased in inflamed intestinal tissues of patients with IBD. Loss-of-function variants of the IL23-receptor gene (IL23R) protect against IBD, and, in animals, blocking IL23 reduces the severity of colitis. These findings indicated that the IL23 and Th17 cell pathways might be promising targets for the treatment of IBD. Clinical trials have investigated the effects of agents designed to target distinct levels of the IL23 and Th17 cell pathways, and the results are providing insights into IBD pathogenesis and additional strategies for modulating these pathways. Strategies to reduce levels of proinflammatory cytokines more broadly and increase anti-inflammatory mechanisms also are emerging for the treatment of IBD. The results from trials targeting these immune system pathways have provided important lessons for future trials. Findings indicate the importance of improving approaches to integrate patient features and biomarkers of response with selection of therapeutics.

• Authors: Clara Abraham, Parambir S Dulai, Séverine Vermeire, William J Sandborn
• Journal: Gastroenterology (Gastroenterology) Vol. 152 Issue 2 Pg. 374-388.e4 (02 2017) ISSN: 1528-0012 [Electronic] United States
• PMID: 27780712 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Cytokines
• Interleukin-23
• Lysophospholipids
• Oligonucleotides
• Piperidines
• Protein Kinase Inhibitors
• Pyrimidines
• Pyrroles
• Smad7 Protein
• Transforming Growth Factor beta
• sphingosine 1-phosphate
• fontolizumab
• tofacitinib
• risankizumab
• briakinumab
• secukinumab
• Janus Kinases
• Ustekinumab
• Sphingosine
• GED0301

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Cytokines (immunology)
• Humans
• Inflammatory Bowel Diseases (drug therapy, immunology)
• Interleukin-23 (immunology)
• Janus Kinases (immunology)
• Lysophospholipids (immunology)
• Molecular Targeted Therapy
• Oligonucleotides (therapeutic use)
• Piperidines (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines (therapeutic use)
• Pyrroles (therapeutic use)
• Signal Transduction
• Smad7 Protein (immunology)
• Sphingosine (analogs & derivatives, immunology)
• Th17 Cells (immunology)
• Transforming Growth Factor beta (immunology)
• Ustekinumab (therapeutic use)