Title:Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases
Volume: 21
Issue: 17
Author(s): Donna Finch and Matthew Sleeman
Affiliation:
Keywords:
Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
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.