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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases

Author(s): Donna Finch and Matthew Sleeman

Volume 21, Issue 17, 2015

Page: [2198 - 2205] Pages: 8

DOI: 10.2174/1381612821666150310144603

Price: $65


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.

Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.

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