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.
Keywords: Interleukin, interleukin-1, inflammasome, rheumatology, cryopyrin, gout, arthritis, CAPS.
Current Pharmaceutical Design
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.
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Cite this article as:
Finch Donna and Sleeman Matthew, Finding a Place for Interleukin-1 Inhibitors in the Treatment of Rheumatologic Diseases, Current Pharmaceutical Design 2015; 21 (17) . https://dx.doi.org/10.2174/1381612821666150310144603
DOI https://dx.doi.org/10.2174/1381612821666150310144603 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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