Finding a place for interleukin-1 inhibitors in the treatment of rheumatologic diseases.

Abstract

Interleukin-1 inhibitors were tested in large arthritis trials with less than impressive results, despite having convincing disease expression data and pre-clinical animal model supporting the potential pathogenic role of this cytokine in these settings. Despite disappointing beginnings, some IL-1 pathway blocking drugs are now beginning to find a place in the pharmacopoeia of rheumatologists. Drug developers utilised rapidly growing understanding of the molecular pathway and the genetic basis of key diseases to seek out conditions in which IL-1 pathway activation was much more likely to have a pivotal role in disease pathogenesis compared to the major arthritides. This review details the crucial advances in understanding of the IL-1 pathway activation which enabled this progress, particularly the advent of inflammasome biology. The drug development of IL-1 biologics in rheumatological diseases makes a fascinating case study illustrating major changes in drug development strategy encompassing closer synergies between translational biology, underlying molecular pathophysiology of disease, and novel clinical development pathways of biologic therapeutics.

• Authors: Donna Finch, Matthew Sleeman
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 21 Issue 17 Pg. 2198-205 ( 2015) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 25760298 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Interleukin-1

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• Humans
• Interleukin-1 (antagonists & inhibitors, metabolism)